Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by immune dysregulation and multi-organ damage. Recent advances have underscored the critical involvement of extracellular matrix (ECM) biophysical properties in shaping immune cell behavior and metabolic states that contribute to disease progression. This review systematically delineates the pathological remodeling of ECM biophysics in SLE, with a focus on their roles in mechanotransduction, immune-metabolic interplay, and organ-specific tissue injury. By integrating current evidence, we highlight how ECM-derived mechanical cues orchestrate aberrant immune responses and propose new perspectives for targeting ECM-immune crosstalk in the development of organ-specific, mechanism-based therapies for SLE.
Citation: Qiwei Li, Qiang Li, Zhaoyang Xiao, Keiji NARUSE, Ken Takahashi. Biophysical regulation of extracellular matrix in systemic lupus erythematosus[J]. AIMS Biophysics, 2025, 12(3): 412-437. doi: 10.3934/biophy.2025020
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by immune dysregulation and multi-organ damage. Recent advances have underscored the critical involvement of extracellular matrix (ECM) biophysical properties in shaping immune cell behavior and metabolic states that contribute to disease progression. This review systematically delineates the pathological remodeling of ECM biophysics in SLE, with a focus on their roles in mechanotransduction, immune-metabolic interplay, and organ-specific tissue injury. By integrating current evidence, we highlight how ECM-derived mechanical cues orchestrate aberrant immune responses and propose new perspectives for targeting ECM-immune crosstalk in the development of organ-specific, mechanism-based therapies for SLE.
Activation-induced cytidine deaminase
protein kinase B
arginase 1
B lymphocyte-induced maturation protein-1
helper T Cells
C-X-C motif chemokine ligand 13
cationic amino acid transporter 1
CD40 ligand
chronic obstructive pulmonary disease
class switch recombination
cytotoxic T lymphocytes
cathepsin B
extracellular matrix
elastin-derived peptides
elastin receptors
focal adhesion kinase
fibroblastic reticular cells
glomerular basement membrane
hyaluronic acid
heparan sulfate
interferon-alpha
interstitial fluid pressure
inhibitor of kappa B
IκB kinase
interleukin-6
interleukin-7
interleukin-10
inducible nitric oxide synthase
lupus nephritis
latent transforming growth factor-β binding protein 2
lymphoproliferation
matrix metalloproteinase-9
Murphy Roths large mouse
nuclear factor kappa-light-chain-enhancer of activated B cells
natural killer
nitric oxide
osteoarthritis
plasmacytoid dendritic cells
platelet-derived growth factor
platelet factor 4
phosphoinositide 3-kinase
rheumatoid arthritis
arginine-glycine-aspartic acid
systemic lupus erythematosus
secreted phosphoprotein 1
systemic sclerosis
shear wave elastography
transcriptional co-activator with PDZ-binding motif
TEA domain family transcription factors
T follicular helper cell
transforming growth factor-beta
TGF-β receptor II
Toll-like receptor 2
Toll-like receptor 4
tumor necrosis factor
TNF receptor-associated factors
triggering receptor expressed on myeloid cells 2
vascular cell adhesion molecule-1
Yes-associated protein
| [1] | Hoi A, Igel T, Mok CC, et al. (2024) Systemic lupus erythematosus. Lancet 403: 2326-2338. http://dx.doi.org/10.1016/S0140-6736(24)00398-2 |
| [2] | Sciascia S, Cozzi M, Barinotti A, et al. (2022) Renal fibrosis in lupus nephritis. Int J Mol Sci 23: 14317. http://dx.doi.org/10.3390/ijms232214317 |
| [3] | Gheita TA, Abdel Rehim DM, Kenawy SA, et al. (2015) Clinical significance of matrix metalloproteinase-3 in systemic lupus erythematosus patients: a potential biomarker for disease activity and damage. Acta Reumatol Port 40: 145-149. |
| [4] | Genovese F, Akhgar A, Lim SS, et al. (2021) Collagen type III and VI remodeling biomarkers are associated with kidney fibrosis in lupus nephritis. Kidney360 2: 1473-1481. http://dx.doi.org/10.34067/KID.0001132021 |
| [5] | Elosegui-Artola A (2021) The extracellular matrix viscoelasticity as a regulator of cell and tissue dynamics. Curr Opin Cell Biol 72: 10-18. http://dx.doi.org/10.1016/j.ceb.2021.04.002 |
| [6] | Tiskratok W, Chuinsiri N, Limraksasin P, et al. (2025) Extracellular matrix stiffness: mechanotransduction and mechanobiological response-driven strategies for biomedical applications targeting fibroblast inflammation. Polymers (Basel) 17: 822. http://dx.doi.org/10.3390/polym17060822 |
| [7] | Kolios AGA, Tsokos GC (2021) Skin-kidney crosstalk in SLE. Nat Rev Rheumatol 17: 253-254. http://dx.doi.org/10.1038/s41584-021-00588-0 |
| [8] | Embry AE, Mohammadi H, Niu X, et al. (2016) Biochemical and cellular determinants of renal glomerular elasticity. Plos One 11: e0167924. http://dx.doi.org/10.1371/journal.pone.0167924 |
| [9] | Wyss HM, Henderson JM, Byfield FJ, et al. (2011) Biophysical properties of normal and diseased renal glomeruli. Am J Physiol Cell Physiol 300: C397-405. http://dx.doi.org/10.1152/ajpcell.00438.2010 |
| [10] | Sridharan A, Rajan SD, Muthuswamy J (2013) Long-term changes in the material properties of brain tissue at the implant-tissue interface. J Neural Eng 10: 066001. http://dx.doi.org/10.1088/1741-2560/10/6/066001 |
| [11] | Akhmanova M, Osidak E, Domogatsky S, et al. (2015) Physical, spatial, and molecular aspects of extracellular matrix of in vivo niches and artificial scaffolds relevant to stem cells research. Stem Cells Int 2015: 167025. http://dx.doi.org/10.1155/2015/167025 |
| [12] | Umut Ozcan M, Ocal S, Basdogan C, et al. (2011) Characterization of frequency-dependent material properties of human liver and its pathologies using an impact hammer. Med Image Anal 15: 45-52. http://dx.doi.org/10.1016/j.media.2010.06.010 |
| [13] | Ishihara S, Haga H (2022) Matrix stiffness contributes to cancer progression by regulating transcription factors. Cancers (Basel) 14: 1049. http://dx.doi.org/10.3390/cancers14041049 |
| [14] | Samir AE, Allegretti AS, Zhu Q, et al. (2015) Shear wave elastography in chronic kidney disease: a pilot experience in native kidneys. BMC Nephrol 16: 119. http://dx.doi.org/10.1186/s12882-015-0120-7 |
| [15] | Alexander JJ, Zwingmann C, Jacob A, et al. (2007) Alteration in kidney glucose and amino acids are implicated in renal pathology in MRL/lpr mice. Biochim Biophys Acta 1772: 1143-1149. http://dx.doi.org/10.1016/j.bbadis.2007.07.002 |
| [16] | Lee MS, Cho JY, Moon MH, et al. (2024) Comprehensive ultrasonographic evaluation of normal and fibrotic kidneys in a mouse model with an ultra-high-frequency transducer. Ultrasonography 43: 314-326. http://dx.doi.org/10.14366/usg.24024 |
| [17] | Hu M, Yao Z, Xu L, et al. (2023) M2 macrophage polarization in systemic sclerosis fibrosis: pathogenic mechanisms and therapeutic effects. Heliyon 9: e16206. http://dx.doi.org/10.1016/j.heliyon.2023.e16206 |
| [18] | Castellano F, Molinier-Frenkel V (2020) Control of T-cell activation and signaling by amino-acid catabolizing enzymes. Front Cell Dev Biol 8: 613416. http://dx.doi.org/10.3389/fcell.2020.613416 |
| [19] | Tharp KM, Kersten K, Maller O, et al. (2024) Tumor-associated macrophages restrict CD8(+) T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment. Nat Cancer 5: 1045-1062. http://dx.doi.org/10.1038/s43018-024-00775-4 |
| [20] | Meli VS, Atcha H, Veerasubramanian PK, et al. (2020) YAP-mediated mechanotransduction tunes the macrophage inflammatory response. Sci Adv 6: eabb8471. http://dx.doi.org/10.1126/sciadv.abb8471 |
| [21] | Cai G, Lu Y, Zhong W, et al. (2023) Piezo1-mediated M2 macrophage mechanotransduction enhances bone formation through secretion and activation of transforming growth factor-beta1. Cell Prolif 56: e13440. http://dx.doi.org/10.1111/cpr.13440 |
| [22] | Atcha H, Jairaman A, Holt JR, et al. (2021) Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat Commun 12: 3256. http://dx.doi.org/10.1038/s41467-021-23482-5 |
| [23] | Mei F, Guo Y, Wang Y, et al. (2024) Matrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis. Cell Prolif 57: e13640. http://dx.doi.org/10.1111/cpr.13640 |
| [24] | Asosingh K, Lauruschkat CD, Alemagno M, et al. (2020) Arginine metabolic control of airway inflammation. JCI Insight 5: e127801. http://dx.doi.org/10.1172/jci.insight.127801 |
| [25] | Lu Y, Hao C, Yu S, et al. (2022) Cationic amino acid transporter-1 (CAT-1) promotes fibroblast-like synoviocyte proliferation and cytokine secretion by taking up L-arginine in rheumatoid arthritis. Arthritis Res Ther 24: 234. http://dx.doi.org/10.1186/s13075-022-02921-8 |
| [26] | Pesce JT, Ramalingam TR, Mentink-Kane MM, et al. (2009) Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. Plos Pathog 5: e1000371. http://dx.doi.org/10.1371/journal.ppat.1000371 |
| [27] | Bradshaw AD, DeLeon-Pennell KY (2020) T-cell regulation of fibroblasts and cardiac fibrosis. Matrix Biol 91–92: 167-175. http://dx.doi.org/10.1016/j.matbio.2020.04.001 |
| [28] | Caster DJ, Merchant ML (2021) Collagen remodeling biomarkers in lupus nephritis. Kidney360 2: 1395-1398. http://dx.doi.org/10.34067/KID.0004732021 |
| [29] | Tveita A, Rekvig OP, Zykova SN (2008) Glomerular matrix metalloproteinases and their regulators in the pathogenesis of lupus nephritis. Arthritis Res Ther 10: 229. http://dx.doi.org/10.1186/ar2532 |
| [30] | Suarez-Fueyo A, Tsokos MG, Kwok SK, et al. (2019) Hyaluronic acid synthesis contributes to tissue damage in systemic lupus erythematosus. Front Immunol 10: 2172. http://dx.doi.org/10.3389/fimmu.2019.02172 |
| [31] | Wei R, Gao B, Shih F, et al. (2017) Alterations in urinary collagen peptides in lupus nephritis subjects correlate with renal dysfunction and renal histopathology. Nephrol Dial Transplant 32: 1468-1477. http://dx.doi.org/10.1093/ndt/gfw446 |
| [32] | Olin AI, Morgelin M, Truedsson L, et al. (2014) Pathogenic mechanisms in lupus nephritis: Nucleosomes bind aberrant laminin beta1 with high affinity and colocalize in the electron-dense deposits. Arthritis Rheumatol 66: 397-406. http://dx.doi.org/10.1002/art.38250 |
| [33] | Tyler EJ, Pearce OMT (2024) Tumor's digest: Macrophage metabolism creates a barrier to T cells. Cancer Res 84: 3322-3323. http://dx.doi.org/10.1158/0008-5472.CAN-24-3039 |
| [34] | Lee M, Du H, Winer DA, et al. (2022) Mechanosensing in macrophages and dendritic cells in steady-state and disease. Front Cell Dev Biol 10: 1044729. http://dx.doi.org/10.3389/fcell.2022.1044729 |
| [35] | Chakraborty M, Chu K, Shrestha A, et al. (2021) Mechanical stiffness controls dendritic cell metabolism and function. Cell Rep 34: 108609. http://dx.doi.org/10.1016/j.celrep.2020.108609 |
| [36] | Spriet LL, Howlett RA, Heigenhauser GJ (2000) An enzymatic approach to lactate production in human skeletal muscle during exercise. Med Sci Sports Exerc 32: 756-763. http://dx.doi.org/10.1097/00005768-200004000-00007 |
| [37] | Lewis JS, Dolgova NV, Chancellor TJ, et al. (2013) The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates. Biomaterials 34: 9063-9070. http://dx.doi.org/10.1016/j.biomaterials.2013.08.021 |
| [38] | Means TK, Latz E, Hayashi F, et al. (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115: 407-417. http://dx.doi.org/10.1172/JCI23025 |
| [39] | Baechler EC, Batliwalla FM, Karypis G, et al. (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA 100: 2610-2615. http://dx.doi.org/10.1073/pnas.0337679100 |
| [40] | Morgado FN, da Silva AVA, Porrozzi R (2020) Infectious diseases and the lymphoid extracellular matrix remodeling: a focus on conduit system. Cells 9: 725. http://dx.doi.org/10.3390/cells9030725 |
| [41] | Savitri C, Ha SS, Kwon JW, et al. (2024) Human fibroblast-derived matrix hydrogel accelerates regenerative wound remodeling through the interactions with macrophages. Adv Sci (Weinh) 11: e2305852. http://dx.doi.org/10.1002/advs.202305852 |
| [42] | Adu-Berchie K, Liu Y, Zhang DKY, et al. (2023) Generation of functionally distinct T-cell populations by altering the viscoelasticity of their extracellular matrix. Nat Biomed Eng 7: 1374-1391. http://dx.doi.org/10.1038/s41551-023-01052-y |
| [43] | Li Y, Hu MX, Yan M, et al. (2023) Intestinal models based on biomimetic scaffolds with an ECM micro-architecture and intestinal macro-elasticity: close to intestinal tissue and immune response analysis. Biomater Sci 11: 567-582. http://dx.doi.org/10.1039/d2bm01051h |
| [44] | Bhattacharjee O, Ayyangar U, Kurbet AS, et al. (2019) Unraveling the ECM-immune cell crosstalk in skin diseases. Front Cell Dev Biol 7: 68. http://dx.doi.org/10.3389/fcell.2019.00068 |
| [45] | Diehl R, Hubner S, Lehr S, et al. (2025) Skin deep and beyond: unravelling B cell extracellular matrix interactions in cutaneous immunity and disease. Exp Dermatol 34: e70068. http://dx.doi.org/10.1111/exd.70068 |
| [46] | Pathni A, Wagh K, Rey-Suarez I, et al. (2024) Mechanical regulation of lymphocyte activation and function. J Cell Sci 137: jcs219030. http://dx.doi.org/10.1242/jcs.219030 |
| [47] | Wan Z, Zhang S, Fan Y, et al. (2013) B cell activation is regulated by the stiffness properties of the substrate presenting the antigens. J Immunol 190: 4661-4675. http://dx.doi.org/10.4049/jimmunol.1202976 |
| [48] | Oudart JB, Doue M, Vautrin A, et al. (2016) The anti-tumor NC1 domain of collagen XIX inhibits the FAK/ PI3K/Akt/mTOR signaling pathway through alphavbeta3 integrin interaction. Oncotarget 7: 1516-1528. http://dx.doi.org/10.18632/oncotarget.6399 |
| [49] | Valdivia A, Avalos AM, Leyton L (2023) Thy-1 (CD90)-regulated cell adhesion and migration of mesenchymal cells: insights into adhesomes, mechanical forces, and signaling pathways. Front Cell Dev Biol 11: 1221306. http://dx.doi.org/10.3389/fcell.2023.1221306 |
| [50] | Fiore VF, Wong SS, Tran C, et al. (2018) alphavbeta3 Integrin drives fibroblast contraction and strain stiffening of soft provisional matrix during progressive fibrosis. JCI Insight 3: e97597. http://dx.doi.org/10.1172/jci.insight.97597 |
| [51] | Zhang L, Dong Y, Dong Y, et al. (2012) Role of integrin-beta3 protein in macrophage polarization and regeneration of injured muscle. J Biol Chem 287: 6177-6186. http://dx.doi.org/10.1074/jbc.M111.292649 |
| [52] | Hu Q, Saleem K, Pandey J, et al. (2023) Cell adhesion molecules in fibrotic diseases. Biomedicines 11: 1995. http://dx.doi.org/10.3390/biomedicines11071995 |
| [53] | Takada YK, Shimoda M, Maverakis E, et al. (2021) Soluble CD40L activates soluble and cell-surface integrin alphavbeta3, alpha5beta1, and alpha4beta1 by binding to the allosteric ligand-binding site (site 2). J Biol Chem 296: 100399. http://dx.doi.org/10.1016/j.jbc.2021.100399 |
| [54] | Gray D, Siepmann K, Wohlleben G (1994) CD40 ligation in B cell activation, isotype switching and memory development. Semin Immunol 6: 303-310. http://dx.doi.org/10.1006/smim.1994.1039 |
| [55] | Gerdes N, Seijkens T, Lievens D, et al. (2016) Platelet CD40 exacerbates atherosclerosis by transcellular activation of endothelial cells and leukocytes. Arterioscler Thromb Vasc Biol 36: 482-490. http://dx.doi.org/10.1161/ATVBAHA.115.307074 |
| [56] | Michel NA, Zirlik A, Wolf D (2017) CD40L and its receptors in atherothrombosis-an update. Front Cardiovasc Med 4: 40. http://dx.doi.org/10.3389/fcvm.2017.00040 |
| [57] | So T, Nagashima H, Ishii N (2015) TNF receptor-associated factor (TRAF) signaling network in CD4(+) T-lymphocytes. Tohoku J Exp Med 236: 139-154. http://dx.doi.org/10.1620/tjem.236.139 |
| [58] | Devin A, Lin Y, Yamaoka S, et al. (2001) The alpha and beta subunits of IkappaB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF. Mol Cell Biol 21: 3986-3994. http://dx.doi.org/10.1128/MCB.21.12.3986-3994.2001 |
| [59] | Zhang W, Shi Q, Xu X, et al. (2012) Aberrant CD40-induced NF-kappaB activation in human lupus B lymphocytes. Plos One 7: e41644. http://dx.doi.org/10.1371/journal.pone.0041644 |
| [60] | Karnell JL, Rieder SA, Ettinger R, et al. (2019) Targeting the CD40-CD40L pathway in autoimmune diseases: humoral immunity and beyond. Adv Drug Deliv Rev 141: 92-103. http://dx.doi.org/10.1016/j.addr.2018.12.005 |
| [61] | Nicastro L, Tukel C (2019) Bacterial amyloids: the link between bacterial infections and autoimmunity. Trends Microbiol 27: 954-963. http://dx.doi.org/10.1016/j.tim.2019.07.002 |
| [62] | Takada Y, Fujita M, Takada YK (2023) Virtual screening of protein data bank via docking simulation identified the role of integrins in growth factor signaling, the allosteric activation of integrins, and P-selectin as a new integrin ligand. Cells 12: 2265. http://dx.doi.org/10.3390/cells12182265 |
| [63] | Vijver SV, Singh A, Mommers-Elshof E, et al. (2021) Collagen fragments produced in cancer mediate T cell suppression through leukocyte-associated immunoglobulin-like receptor 1. Front Immunol 12: 733561. http://dx.doi.org/10.3389/fimmu.2021.733561 |
| [64] | Batsalova T, Dzhambazov B (2023) Significance of type II collagen posttranslational modifications: from autoantigenesis to improved diagnosis and treatment of rheumatoid arthritis. Int J Mol Sci 24: 9884. http://dx.doi.org/10.3390/ijms24129884 |
| [65] | Mjelle JE, Rekvig OP, Fenton KA (2007) Nucleosomes possess a high affinity for glomerular laminin and collagen IV and bind nephritogenic antibodies in murine lupus-like nephritis. Ann Rheum Dis 66: 1661-1668. http://dx.doi.org/10.1136/ard.2007.070482 |
| [66] | Dart ML, Jankowska-Gan E, Huang G, et al. (2010) Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis. Circ Res 107: 1106-1116. http://dx.doi.org/10.1161/CIRCRESAHA.110.221069 |
| [67] | Antoniel M, Traina F, Merlini L, et al. (2020) Tendon extracellular matrix remodeling and defective cell polarization in the presence of collagen VI mutations. Cells 9: 409. http://dx.doi.org/10.3390/cells9020409 |
| [68] | Grabell DA, Matthews LA, Yancey KB, et al. (2015) Detection of type VII collagen autoantibodies before the onset of bullous systemic lupus erythematosus. JAMA Dermatol 151: 539-543. http://dx.doi.org/10.1001/jamadermatol.2014.4409 |
| [69] | Rasi K, Piuhola J, Czabanka M, et al. (2010) Collagen XV is necessary for modeling of the extracellular matrix and its deficiency predisposes to cardiomyopathy. Circ Res 107: 1241-1252. http://dx.doi.org/10.1161/CIRCRESAHA.110.222133 |
| [70] | Hamano Y, Okude T, Shirai R, et al. (2010) Lack of collagen XVIII/endostatin exacerbates immune-mediated glomerulonephritis. J Am Soc Nephrol 21: 1445-1455. http://dx.doi.org/10.1681/ASN.2009050492 |
| [71] | Salmon H, Franciszkiewicz K, Damotte D, et al. (2012) Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J Clin Invest 122: 899-910. http://dx.doi.org/10.1172/JCI45817 |
| [72] | Yuan Z, Li Y, Zhang S, et al. (2023) Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments. Mol Cancer 22: 48. http://dx.doi.org/10.1186/s12943-023-01744-8 |
| [73] | Hartmann N, Giese NA, Giese T, et al. (2014) Prevailing role of contact guidance in intrastromal T-cell trapping in human pancreatic cancer. Clin Cancer Res 20: 3422-3433. http://dx.doi.org/10.1158/1078-0432.CCR-13-2972 |
| [74] | Moreau JF, Pradeu T, Grignolio A, et al. (2017) The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans. Ageing Res Rev 35: 322-335. http://dx.doi.org/10.1016/j.arr.2016.11.005 |
| [75] | Fletcher AL, Baker AT, Lukacs-Kornek V, et al. (2020) The fibroblastic T cell niche in lymphoid tissues. Curr Opin Immunol 64: 110-116. http://dx.doi.org/10.1016/j.coi.2020.04.007 |
| [76] | Krishnamurty AT, Turley SJ (2020) Lymph node stromal cells: cartographers of the immune system. Nat Immunol 21: 369-380. http://dx.doi.org/10.1038/s41590-020-0635-3 |
| [77] | Riedel A, Shorthouse D, Haas L, et al. (2016) Tumor-induced stromal reprogramming drives lymph node transformation. Nat Immunol 17: 1118-1127. http://dx.doi.org/10.1038/ni.3492 |
| [78] | Kurotsu S, Sadahiro T, Fujita R, et al. (2020) Soft matrix promotes cardiac reprogramming via inhibition of YAP/TAZ and suppression of fibroblast signatures. Stem Cell Reports 15: 612-628. http://dx.doi.org/10.1016/j.stemcr.2020.07.022 |
| [79] | Li H, Raghunathan V, Stamer WD, et al. (2022) Extracellular matrix stiffness and TGFbeta2 regulate YAP/TAZ activity in human trabecular meshwork cells. Front Cell Dev Biol 10: 844342. http://dx.doi.org/10.3389/fcell.2022.844342 |
| [80] | Fu Y, Wan P, Zhang J, et al. (2021) Targeting mechanosensitive piezo1 alleviated renal fibrosis through p38MAPK-YAP pathway. Front Cell Dev Biol 9: 741060. http://dx.doi.org/10.3389/fcell.2021.741060 |
| [81] | Wang K, Wen D, Xu X, et al. (2023) Extracellular matrix stiffness–The central cue for skin fibrosis. Front Mol Biosci 10: 1132353. http://dx.doi.org/10.3389/fmolb.2023.1132353 |
| [82] | Sapudom J, Alatoom A, Tipay PS, et al. (2025) Matrix stiffening from collagen fibril density and alignment modulates YAP-mediated T-cell immune suppression. Biomaterials 315: 122900. http://dx.doi.org/10.1016/j.biomaterials.2024.122900 |
| [83] | Xiong J, Xiao R, Zhao J, et al. (2024) Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy. J Transl Med 22: 85. http://dx.doi.org/10.1186/s12967-023-04810-3 |
| [84] | Saxena V, Lienesch DW, Zhou M, et al. (2008) Dual roles of immunoregulatory cytokine TGF-beta in the pathogenesis of autoimmunity-mediated organ damage. J Immunol 180: 1903-1912. http://dx.doi.org/10.4049/jimmunol.180.3.1903 |
| [85] | Tsantikos E, Maxwell MJ, Putoczki T, et al. (2013) Interleukin-6 trans-signaling exacerbates inflammation and renal pathology in lupus-prone mice. Arthritis Rheum 65: 2691-2702. http://dx.doi.org/10.1002/art.38061 |
| [86] | Meng XM, Huang XR, Chung AC, et al. (2010) Smad2 protects against TGF-beta/Smad3-mediated renal fibrosis. J Am Soc Nephrol 21: 1477-1487. http://dx.doi.org/10.1681/ASN.2009121244 |
| [87] | Sureshbabu A, Muhsin SA, Choi ME (2016) TGF-beta signaling in the kidney: profibrotic and protective effects. Am J Physiol Renal Physiol 310: F596-F606. http://dx.doi.org/10.1152/ajprenal.00365.2015 |
| [88] | O'Reilly S, Ciechomska M, Cant R, et al. (2014) Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-beta (TGF-beta) signaling promoting SMAD3 activation and fibrosis via Gremlin protein. J Biol Chem 289: 9952-9960. http://dx.doi.org/10.1074/jbc.M113.545822 |
| [89] | Fielding CA, Jones GW, McLoughlin RM, et al. (2014) Interleukin-6 signaling drives fibrosis in unresolved inflammation. Immunity 40: 40-50. http://dx.doi.org/10.1016/j.immuni.2013.10.022 |
| [90] | Triantafyllopoulou A, Franzke CW, Seshan SV, et al. (2010) Proliferative lesions and metalloproteinase activity in murine lupus nephritis mediated by type I interferons and macrophages. Proc Natl Acad Sci USA 107: 3012-3017. http://dx.doi.org/10.1073/pnas.0914902107 |
| [91] | Zhang X, Zhou Y, Yu X, et al. (2019) Differential roles of cysteinyl cathepsins in TGF-beta signaling and tissue fibrosis. iScience 19: 607-622. http://dx.doi.org/10.1016/j.isci.2019.08.014 |
| [92] | Moreland LW, Gay RE, Gay S (1991) Collagen autoantibodies in patients with vasculitis and systemic lupus erythematosus. Clin Immunol Immunopathol 60: 412-418. http://dx.doi.org/10.1016/0090-1229(91)90097-t |
| [93] | Florea F, Bernards C, Caproni M, et al. (2014) Ex vivo pathogenicity of anti-laminin gamma1 autoantibodies. Am J Pathol 184: 494-506. http://dx.doi.org/10.1016/j.ajpath.2013.10.019 |
| [94] | Atta MS, Powell RJ, Todd I (1994) The influence of anti-fibronectin antibodies on interactions involving extracellular matrix components and cells: a possible pathogenic mechanism. Clin Exp Immunol 96: 26-30. http://dx.doi.org/10.1111/j.1365-2249.1994.tb06224.x |
| [95] | Nonaka R, Iesaki T, Kerever A, et al. (2021) Increased risk of aortic dissection with perlecan deficiency. Int J Mol Sci 23: 315. http://dx.doi.org/10.3390/ijms23010315 |
| [96] | van Bruggen MC, Kramers C, Hylkema MN, et al. (1996) Significance of anti-nuclear and anti-extracellular matrix autoantibodies for albuminuria in murine lupus nephritis; a longitudinal study on plasma and glomerular eluates in MRL/l mice. Clin Exp Immunol 105: 132-139. http://dx.doi.org/10.1046/j.1365-2249.1996.d01-731.x |
| [97] | Kozlova N, Grossman JE, Iwanicki MP, et al. (2020) The interplay of the extracellular matrix and stromal cells as a drug target in stroma-rich cancers. Trends Pharmacol Sci 41: 183-198. http://dx.doi.org/10.1016/j.tips.2020.01.001 |
| [98] | Bhattacharya M, Ramachandran P (2023) Immunology of human fibrosis. Nat Immunol 24: 1423-1433. http://dx.doi.org/10.1038/s41590-023-01551-9 |
| [99] | Okada Y (2000) Matrix-degrading metalloproteinases and their roles in joint destruction. Mod Rheumatol 10: 121-128. http://dx.doi.org/10.3109/s101650070018 |
| [100] | Tolboom TC, Pieterman E, van der Laan WH, et al. (2002) Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10. Ann Rheum Dis 61: 975-980. http://dx.doi.org/10.1136/ard.61.11.975 |
| [101] | Ferreira RC, Freitag DF, Cutler AJ, et al. (2013) Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. Plos Genet 9: e1003444. http://dx.doi.org/10.1371/journal.pgen.1003444 |
| [102] | Lee A, Qiao Y, Grigoriev G, et al. (2013) Tumor necrosis factor alpha induces sustained signaling and a prolonged and unremitting inflammatory response in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 65: 928-938. http://dx.doi.org/10.1002/art.37853 |
| [103] | Rudnik M, Hukara A, Kocherova I, et al. (2021) Elevated fibronectin levels in profibrotic CD14(+) monocytes and CD14(+) macrophages in systemic sclerosis. Front Immunol 12: 642891. http://dx.doi.org/10.3389/fimmu.2021.642891 |
| [104] | Liu T, Zhang J (2008) Expression and distribution of type I, III and V collagens in skin lesions from patients with systemic sclerosis. Sichuan Da Xue Xue Bao Yi Xue Ban 39: 748-752. |
| [105] | Timar O, Soltesz P, Szamosi S, et al. (2008) Increased arterial stiffness as the marker of vascular involvement in systemic sclerosis. J Rheumatol 35: 1329-1333. |
| [106] | Mimura Y, Ihn H, Jinnin M, et al. (2005) Constitutive phosphorylation of focal adhesion kinase is involved in the myofibroblast differentiation of scleroderma fibroblasts. J Invest Dermatol 124: 886-892. http://dx.doi.org/10.1111/j.0022-202X.2005.23701.x |
| [107] | Verrecchia F, Mauviel A, Farge D (2006) Transforming growth factor-beta signaling through the Smad proteins: role in systemic sclerosis. Autoimmun Rev 5: 563-569. http://dx.doi.org/10.1016/j.autrev.2006.06.001 |
| [108] | Wang L, Law HKW (2019) Immune complexes impaired glomerular endothelial cell functions in lupus nephritis. Int J Mol Sci 20: 5281. http://dx.doi.org/10.3390/ijms20215281 |
| [109] | Krane SM, Conca W, Stephenson ML, et al. (1990) Mechanisms of matrix degradation in rheumatoid arthritis. Ann N Y Acad Sci 580: 340-354. http://dx.doi.org/10.1111/j.1749-6632.1990.tb17943.x |
| [110] | Kanaoka M, Yamaguchi Y, Komitsu N, et al. (2018) Pro-fibrotic phenotype of human skin fibroblasts induced by periostin via modulating TGF-beta signaling. J Dermatol Sci 90: 199-208. http://dx.doi.org/10.1016/j.jdermsci.2018.02.001 |
| [111] | Dipali SS, King CD, Rose JP, et al. (2023) Proteomic quantification of native and ECM-enriched mouse ovaries reveals an age-dependent fibro-inflammatory signature. Aging (Albany NY) 15: 10821-10855. http://dx.doi.org/10.18632/aging.205190 |
| [112] | Fabre T, Barron AMS, Christensen SM, et al. (2023) Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation. Sci Immunol 8: eadd8945. http://dx.doi.org/10.1126/sciimmunol.add8945 |
| [113] | Ouyang JF, Mishra K, Xie Y, et al. (2023) Systems level identification of a matrisome-associated macrophage polarisation state in multi-organ fibrosis. Elife 12: e85530. http://dx.doi.org/10.7554/eLife.85530 |
| [114] | Chen Y, Bal BS, Gorski JP (1992) Calcium and collagen binding properties of osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 from bone. J Biol Chem 267: 24871-24878. https://doi.org/10.1016/S0021-9258(18)35844-7 |
| [115] | Wong CK, Lit LC, Tam LS, et al. (2005) Elevation of plasma osteopontin concentration is correlated with disease activity in patients with systemic lupus erythematosus. Rheumatology (Oxford) 44: 602-606. http://dx.doi.org/10.1093/rheumatology/keh558 |
| [116] | Faber-Elmann A, Sthoeger Z, Tcherniack A, et al. (2002) Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus. Clin Exp Immunol 127: 393-398. http://dx.doi.org/10.1046/j.1365-2249.2002.01758.x |
| [117] | Zhang Q, Jin H, Chen L, et al. (2019) Effect of ultrasound combined with microbubble therapy on interstitial fluid pressure and VX2 tumor structure in rabbit. Front Pharmacol 10: 716. http://dx.doi.org/10.3389/fphar.2019.00716 |
| [118] | Zhang T, Jia Y, Yu Y, et al. (2022) Targeting the tumor biophysical microenvironment to reduce resistance to immunotherapy. Adv Drug Deliv Rev 186: 114319. http://dx.doi.org/10.1016/j.addr.2022.114319 |
| [119] | Lierova A, Kasparova J, Filipova A, et al. (2022) Hyaluronic acid: known for almost a century, but still in vogue. Pharmaceutics 14: 838. http://dx.doi.org/10.3390/pharmaceutics14040838 |
| [120] | Kreger ST, Voytik-Harbin SL (2009) Hyaluronan concentration within a 3D collagen matrix modulates matrix viscoelasticity, but not fibroblast response. Matrix Biol 28: 336-346. http://dx.doi.org/10.1016/j.matbio.2009.05.001 |
| [121] | Jiang X, Xu S, Miao Y, et al. (2024) Curvature-mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery. Proc Natl Acad Sci USA 121: e2319880121. http://dx.doi.org/10.1073/pnas.2319880121 |
| [122] | Baldari S, Di Modugno F, Nistico P, et al. (2022) Strategies for efficient targeting of tumor collagen for cancer therapy. Cancers (Basel) 14: 4706. http://dx.doi.org/10.3390/cancers14194706 |
| [123] | Aghlara-Fotovat S, Nash A, Kim B, et al. (2021) Targeting the extracellular matrix for immunomodulation: applications in drug delivery and cell therapies. Drug Deliv Transl Res 11: 2394-2413. http://dx.doi.org/10.1007/s13346-021-01018-0 |
| [124] | Azzam M, El Safy S, Abdelgelil SA, et al. (2020) Targeting activated hepatic stellate cells using collagen-binding chitosan nanoparticles for siRNA delivery to fibrotic livers. Pharmaceutics 12: 590. http://dx.doi.org/10.3390/pharmaceutics12060590 |
| [125] | Yang MY, Lin YJ, Han MM, et al. (2022) Pathological collagen targeting and penetrating liposomes for idiopathic pulmonary fibrosis therapy. J Control Release 351: 623-637. http://dx.doi.org/10.1016/j.jconrel.2022.09.054 |
| [126] | Xia Y, Jiang C, Yang M, et al. (2022) SB431542 alleviates lupus nephritis by regulating B cells and inhibiting the TLR9/TGFbeta1/PDGFB signaling. J Autoimmun 132: 102894. http://dx.doi.org/10.1016/j.jaut.2022.102894 |
| [127] | Patrawalla NY, Kajave NS, Albanna MZ, et al. (2023) Collagen and beyond: A comprehensive comparison of human ECM properties derived from various tissue sources for regenerative medicine applications. J Funct Biomater 14: 363. http://dx.doi.org/10.3390/jfb14070363 |
| [128] | Raza IGA, Snelling SJB, Mimpen JY (2024) Defining the extracellular matrix in non-cartilage soft-tissues in osteoarthritis: a systematic review. Bone Joint Res 13: 703-715. http://dx.doi.org/10.1302/2046-3758.1312.BJR-2024-0020.R1 |
| [129] | Kuang H, Shen CR, Jia XY, et al. (2023) Autoantibodies against laminin-521 are pathogenic in anti-glomerular basement membrane disease. Kidney Int 104: 1124-1134. http://dx.doi.org/10.1016/j.kint.2023.07.023 |
| [130] | Watanabe T, Takahashi N, Hirabara S, et al. (2016) Hyaluronan inhibits Tlr-4-dependent RANKL expression in human rheumatoid arthritis synovial fibroblasts. Plos One 11: e0153142. http://dx.doi.org/10.1371/journal.pone.0153142 |
| [131] | Dale MA, Xiong W, Carson JS, et al. (2016) Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization. J Immunol 196: 4536-4543. http://dx.doi.org/10.4049/jimmunol.1502454 |
| [132] | Nastase MV, Janicova A, Roedig H, et al. (2018) Small leucine-rich proteoglycans in renal inflammation: two sides of the coin. J Histochem Cytochem 66: 261-272. http://dx.doi.org/10.1369/0022155417738752 |
| [133] | McCutcheon J, Evans B, D'Cruz DP, et al. (1993) Fibrin deposition in SLE glomerulonephritis. Lupus 2: 99-103. http://dx.doi.org/10.1177/096120339300200206 |
Figures(3) / Tables(2)
Qiwei Li, Qiang Li, Zhaoyang Xiao, Keiji NARUSE, Ken Takahashi. Biophysical regulation of extracellular matrix in systemic lupus erythematosus[J]. AIMS Biophysics, 2025, 12(3): 412-437. doi: 10.3934/biophy.2025020
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