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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAQAgvfp2UONuhG4yhkBN58MFtqelNb6vw1GDSN_l5dJA#_4 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAQAgvfp2UONuhG4yhkBN58MFtqelNb6vw1GDSN_l5dJA#_3 http://www.w3.org/ns/prov#value Hepatocyte growth factor (HGF)/scatter factor (SF) is thought to play an important role in the regeneration of injured gastrointestinal mucosa by promoting the proliferation and migration of epithelial cells. HGF/SF is secreted by stromal cells as an inactive precursor form, and is specifically activated by HGF activator (HGFA) to the active form. HGFA is also produced as a precursor form and activated by thrombin in injured tissues. The activity of HGFA is regulated by two recently identified Kunitz-type serine proteinase inhibitors, namely HGFA inhibitor type 1 (HAI-1) and type 2 (HAI-2). Although the activation of HGF/SF is a critical limiting step in the HGF/SF-induced signaling pathway, little is known about the regulation of HGF/SF activation in injured gastrointestinal mucosa. Immunohistochemically, all these proteins have been detected in gastrointestinal epithelial cells, and HAI-1 was upregulated in regenerative epithelium relative to normal epithelium. During the course of acetic acid-induced murine experimental colitis, HAI-1, but not HAI-2, was indeed upregulated in the recovery phase. In vitro study revealed that HAI-1 is not only an inhibitor, but also a specific cell-surface binding protein, of active HGFA, and acts as a reservoir of this enzyme on the cell surface. Active HGFA/HAI-1 complexes were quickly released from the cell surface by treatment with IL-1beta accompanying significant recovery of HGFA activity in the culture supernatant. These results suggest that HAI-1 is a cell-surface acceptor of activated HGFA in regenerative epithelial cells, and functions on the cell surface to localize the active HGFA that is going to enter the repair process. 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