{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMatrilin‐2 (MATN2) is a multifunctional extracellular matrix (ECM) adapter protein that integrates into filamentous ECM networks through interactions with various collagenous and non‐collagenous proteins, including distinct collagens, fibrillin‐2, fibronectin, and laminin–nidogen complexes. Its modular structure and evolutionarily conserved genomic organization enable it to participate in the assembly and stabilization of supramolecular matrices, as evidenced by its robust binding affinity to collagen type I and its self‐associating capabilities."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cutaneous system, MATN2 is expressed by both keratinocytes and fibroblasts, where it accumulates at the dermal–epidermal junction to support tissue homeostasis and wound healing. Its expression is regulated via the DeltaNp63/BMP-7 signaling axis, which modulates extracellular matrix remodeling during skin repair and influences cell migration in response to injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond normal tissue homeostasis, aberrant MATN2 expression serves as a diagnostic and prognostic biomarker in various diseases. Elevated MATN2 mRNA and protein levels have been reported in pilocytic astrocytoma, suggesting its potential utility in distinguishing indolent from aggressive tumor phenotypes, while its altered expression is also observed in liver disorders—being prominent in the basement membranes of normal liver, perisinusoidal regions in cirrhosis, and neovasculature in hepatocellular carcinoma. Similarly, changes in MATN2 distribution have been noted in calcific aortic valve disease and corneal pathologies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nImmunomodulatory and microbial-interactive functions of MATN2 have also been revealed. In allergic rhinitis, MATN2 is directly targeted by miR-202-5p, affecting regulatory T-cell differentiation and function. Furthermore, MATN2 serves as a binding partner for the Yersinia outer protein YopK, a bacterial effector that modulates host cell adhesion and controls effector translocation via its interaction with surface-exposed MATN2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMATN2 is also implicated as an endogenous danger signal in acute injury scenarios. It is released following burn injury, triggering inflammatory responses, and its expression is markedly induced under high-glucose conditions in mesangial cells through a TGF-β/Smad3-dependent pathway, suggesting a role in the pathogenesis of diabetic nephropathy. Additionally, in radiation-induced pulmonary injury, elevated MATN2 levels activate the p53/p21 axis, leading to reduced cellular proliferation and increased apoptosis in pulmonary epithelial cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nLastly, ocular and oncologic studies further underscore the clinical significance of MATN2. In the aqueous humour of patients with primary angle-closure glaucoma, a downregulation of MATN2 correlates with processes such as inflammation and extracellular matrix remodeling that underlie disease pathology. In ovarian cancer, reduced MATN2 levels are associated with enhanced tumor cell mobility and proliferation, whereas its overexpression interacts with PTEN to suppress the PI3K/AKT pathway, thereby inhibiting tumor growth and suggesting its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dorothea Piecha, Charlotte Wiberg, Matthias Mörgelin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Matrilin-2 interacts with itself and with other extracellular matrix proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20021069"}], "href": "https://doi.org/10.1042/BJ20021069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12180907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12180907"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lajos Mátés, Eva Korpos, Ferenc Déak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative analysis of the mouse and human genes (Matn2 and MATN2) for matrilin-2, a filament-forming protein widely distributed in extracellular matrices."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Matrix Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0945-053x(01)00194-9"}], "href": "https://doi.org/10.1016/s0945-053x(01"}, {"type": "t", "text": "00194-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11852232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11852232"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dorothea Piecha, Karin Hartmann, Birgit Kobbe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of matrilin-2 in human skin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1523-1747.2002.01789.x"}], "href": "https://doi.org/10.1046/j.1523-1747.2002.01789.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12164922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12164922"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tomoe Ichikawa, Yusuke Suenaga, Tadayuki Koda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DeltaNp63/BMP-7-dependent expression of matrilin-2 is involved in keratinocyte migration in response to wounding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.02.128"}], "href": "https://doi.org/10.1016/j.bbrc.2008.02.128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18328806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18328806"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "M K Sharma, M A Watson, M Lyman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Matrilin-2 expression distinguishes clinically relevant subsets of pilocytic astrocytoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/01.wnl.0000188667.66646.1c"}], "href": "https://doi.org/10.1212/01.wnl.0000188667.66646.1c"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16401863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16401863"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Erzsébet Szabó, Eva Korpos, Enkhjargal Batmunkh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of matrilin-2 in liver cirrhosis and hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Oncol Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12253-008-9005-4"}], "href": "https://doi.org/10.1007/s12253-008-9005-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18386166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18386166"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Erlinda The, Qingzhou Yao, Peijian Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells9020385"}], "href": "https://doi.org/10.3390/cells9020385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32046115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32046115"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "László V Módis, Gréta Varkoly, János Bencze, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular matrix changes in corneal opacification vary depending on etiology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2021)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33633437"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33633437"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Li Wang, Xin Yang, Wencai Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-202-5p/MATN2 are associated with regulatory T-cells differentiation and function in allergic rhinitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-019-00266-0"}], "href": "https://doi.org/10.1007/s13577-019-00266-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31493245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31493245"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yafang Tan, Wanbing Liu, Qingwen Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Yersinia pestis YopK Inhibits Bacterial Adhesion to Host Cells by Binding to the Extracellular Matrix Adaptor Protein Matrilin-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/IAI.01069-16"}], "href": "https://doi.org/10.1128/IAI.01069-16"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28533472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28533472"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yunfei Chi, Jiake Chai, Chengfeng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The extracellular matrix protein matrilin-2 induces post-burn inflammatory responses as an endogenous danger signal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflamm Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00011-015-0867-0"}], "href": "https://doi.org/10.1007/s00011-015-0867-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26271809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26271809"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Shukun Zhang, Menglan Zhang, Hong Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2016.04.091"}], "href": "https://doi.org/10.1016/j.bbrc.2016.04.091"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27105914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27105914"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Junming Luo, Menglan Zhang, Hong Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Matrilin-2 regulates proliferation, apoptosis and cell cycle during radiation-induced injury in HPAEpiC cell."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2016.12.022"}], "href": "https://doi.org/10.1016/j.bbrc.2016.12.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27923659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27923659"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Liming Wang, Zhao Xu, Yaru Hong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Low expression of TGF-β2 and matrilin2 in human aqueous humour with acute primary angle closure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.18111"}], "href": "https://doi.org/10.1111/jcmm.18111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38235996"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38235996"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jingbo Liu, Jing Zhang, Yuan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MATN2 overexpression suppresses tumor growth in ovarian cancer via PTEN/PI3K/AKT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Funct Integr Genomics (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10142-024-01340-z"}], "href": "https://doi.org/10.1007/s10142-024-01340-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38568332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38568332"}]}]}]}