{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Hemicentin‐2 (HMCN2) is an evolutionarily conserved extracellular matrix protein belonging to the fibulin family that plays diverse roles in tissue organization and disease. Studies in invertebrates and mammals indicate that hemicentins are secreted proteins that contribute to the stabilization of nascent structures; for example, deposition of hemicentins at the cleavage furrow is essential for successful cytokinesis during early embryonic development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, genetic association studies in human populations have identified HMCN2 as a candidate locus involved in connective tissue disorders such as inguinal hernias, suggesting that alterations in extracellular matrix components may contribute to disease pathogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and, separately, to valve degeneration in bicuspid aortic valve via impacts on calcium metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In mouse models, genetic manipulation of hemicentin orthologs has been used to test the hypothesis that these large ECM proteins help to link basement membranes and coordinate tissue adhesion, a function that is further supported by studies showing complementary cell‐type–specific expression patterns. In these studies, HMCN2 is predominantly produced by epithelial cells at junctional interfaces such as the dermal–epidermal and myotendinous junctions, whereas its paralog HMCN1 is typically produced by mesenchymal cells, indicating that these proteins play distinct yet cooperative roles in maintaining tissue integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its structural functions, altered HMCN2 expression has been linked to lipid-related genetic risk in Alzheimer’s disease, suggesting that changes in ECM dynamics may also influence neurodegenerative processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, studies in zebrafish demonstrate that HMCN2, in conjunction with other fibulin family members, is crucial for epidermal–dermal adhesion and proper migration of mesenchymal cells during fin development, thereby underscoring its role in ECM remodeling and cell signaling during tissue morphogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight a multifaceted role for HMCN2 in extracellular matrix assembly and stabilization, where it not only supports critical developmental processes such as cytokinesis and tissue fusion but also contributes to the susceptibility and pathogenesis of connective tissue disorders and potentially neurodegeneration.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xuehong Xu, Bruce E Vogel "}, {"type": "b", "children": [{"type": "t", "text": "A secreted protein promotes cleavage furrow maturation during cytokinesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2010.12.006"}], "href": "https://doi.org/10.1016/j.cub.2010.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21215633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21215633"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Keiko Hikino, Masaru Koido, Kohei Tomizuka, et al. 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An exome-wide association study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2016.11.012"}], "href": "https://doi.org/10.1016/j.yjmcc.2016.11.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27894865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27894865"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Meei-Hua Lin, Bill D Pope, Takako Sasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.159"}], "href": "https://doi.org/10.1002/dvdy.159"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32035013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32035013"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daniela Welcker, Cornelia Stein, Natalia Martins Feitosa, et al. 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