{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMEP1A encodes the alpha subunit of the zinc-dependent endopeptidase meprin A, a member of the astacin family that is expressed in several epithelial tissues. In human skin, for example, meprin α is predominantly localized in the stratum basale where it appears to contribute to keratinocyte proliferation, while its counterpart, meprin β, localizes to more differentiated layers and is implicated in terminal differentiation. In addition, meprin α is involved in extracellular matrix remodeling by processing procollagens—activities that support both normal tissue homeostasis and dynamic epithelial differentiation. Notably, activation of pro-meprin α occurs via proteolytic cleavage by members of the serine protease family, a process that is modified in pathological contexts such as colorectal cancer, where aberrant activation contributes to a deregulated proteolytic environment."}, {"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": "\nMEP1A’s function has also been linked to the regulation of inflammatory processes. Genetic studies indicate a strong association between variants in MEP1A and inflammatory bowel disease (IBD), particularly ulcerative colitis, with reduced meprin α expression correlating with exacerbated intestinal inflammation in both patient samples and experimental mouse models. In vitro studies further demonstrate that meprin α can modulate inflammatory cytokine levels by cleaving factors such as interleukin-6, thereby influencing downstream signaling events. The expression of MEP1A is subject to regulatory controls, as transcription factors like CDX2—as well as pro-inflammatory cytokines such as TNF-α—can influence its expression during colitis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of malignancy, aberrant expression and activation of meprin α have been implicated in tumor progression. In colorectal cancer, for instance, mislocalized secretion leads to substantial accumulation of active meprin α in the tumor stroma where it promotes cell migration, invasion, and angiogenesis—processes that are mediated, in part, through the proteolytic shedding of growth factor ligands and transactivation of the EGFR signaling pathway. Similar pro-invasive functions have been observed in hepatocellular carcinoma, where meprin α expression is upregulated and contributes to migratory and invasive cell behavior. Furthermore, emerging genetic studies have connected MEP1A polymorphisms with metabolic alterations in conditions such as polycystic ovary syndrome and even predisposition to migraine; these findings point to a broader systemic impact of meprin α function beyond the gastrointestinal tract."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christoph Becker-Pauly, Markus Höwel, Tatjana Walker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The alpha and beta subunits of the metalloprotease meprin are expressed in separate layers of human epidermis, revealing different functions in keratinocyte proliferation and differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.jid.5700675"}], "href": "https://doi.org/10.1038/sj.jid.5700675"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17195012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17195012"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daniel Kronenberg, Bernd C Bruns, Catherine Moali, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Activation of human meprin-alpha in a cell culture model of colorectal cancer is triggered by the plasminogen-activating system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M206203200"}], "href": "https://doi.org/10.1074/jbc.M206203200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12189145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12189145"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "S Banerjee, B Oneda, L M Yap, et al. 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