{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMatrilin‐2 (MATN2) is a versatile extracellular matrix adaptor protein that contributes to the formation of filamentous networks in a wide range of tissues. During embryogenesis, MATN2 is expressed in skeletal and connective tissues, whereas in postnatal life its expression broadens to include epithelial, muscle, nervous, and other connective tissues. Its transcription is governed by alternative promoters—one providing ubiquitous, housekeeping‐like expression and another conferring cell type specificity—supporting a role in both developmental and homeostatic extracellular matrix organization and cell–matrix communication."}, {"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 nervous system, MATN2 acts as a permissive substrate that enhances neurite outgrowth and Schwann cell migration, a function that is critical during both normal development and nerve repair following injury. Moreover, MATN2 can serve as an endogenous danger signal in inflammatory conditions—it is upregulated in injured nerves and, by interacting with Toll‐like receptor 4 (TLR4), triggers proinflammatory gene expression in macrophages. This capacity to modulate innate immune responses implicates MATN2 in processes that contribute to axonal damage in conditions such as multiple sclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its neural roles, MATN2 influences extracellular matrix assembly and cellular proliferation in diverse tissues. It interacts with major matrix components such as collagen, laminin, and fibronectin, and its altered expression is associated with pathological changes observed in osteoarthritis, liver fibrosis, and hepatocarcinogenesis. In the liver, for example, the absence of MATN2 leads to enhanced growth factor signaling (e.g. EGFR and Erk1/2 activation), decreased cell cycle inhibition, and increased β‐catenin expression, thereby predisposing tissue to tumor development. Similarly, MATN2 upregulation following burn injury or irradiation promotes inflammatory responses and induces a p53/p21‐mediated cell cycle arrest in pulmonary epithelial cells. These findings underscore MATN2’s multifaceted role as a modulator of matrix integrity, tissue repair, and cellular proliferation in both physiological and disease contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "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": 2, "children": [{"type": "t", "text": "Andreas R Klatt, Mats Paulsson, Raimund Wagener "}, {"type": "b", "children": [{"type": "t", "text": "Expression of matrilins during maturation of mouse skeletal tissues."}]}, {"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(02)00006-9"}], "href": "https://doi.org/10.1016/s0945-053x(02"}, {"type": "t", "text": "00006-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12009334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12009334"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lajos Mátés, Claudia Nicolae, Matthias Mörgelin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mice lacking the extracellular matrix adaptor protein matrilin-2 develop without obvious abnormalities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Matrix Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.matbio.2004.05.003"}], "href": "https://doi.org/10.1016/j.matbio.2004.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15296947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15296947"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dmitry Malin, Eva Sonnenberg-Riethmacher, Daria Guseva, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Axonally derived matrilin-2 induces proinflammatory responses that exacerbate autoimmune neuroinflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI71385"}], "href": "https://doi.org/10.1172/JCI71385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25329699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25329699"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Alexandra Fullár, Kornélia Baghy, Ferenc Deák, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0093469"}], "href": "https://doi.org/10.1371/journal.pone.0093469"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24691449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24691449"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shukun Zhang, Jinwu Peng, Yan Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Matrilin-2 is a widely distributed extracellular matrix protein and a potential biomarker in the early stage of osteoarthritis in articular cartilage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2014/986127"}], "href": "https://doi.org/10.1155/2014/986127"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24741569"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24741569"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Edith Hintermann, Monika Bayer, Josef M Pfeilschifter, et al. 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