{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T16:45:51Z","timestamp":1770482751082,"version":"3.49.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:p>In human intestinal smooth muscle cells, endogenous insulin-like growth factor-I (IGF-I) regulates growth and IGF-binding protein-5 (IGFBP-5) expression. The effects of IGF-I are facilitated by IGFBP-5. We previously showed that IGFBP-5 acts independently of IGF-I in human intestinal muscle to stimulate proliferation and upregulate IGF-I production by activation of Erk1\/2 and p38 MAPK. Thus a positive feedback loop exists between IGF-I and IGFBP-5, whereby both stimulate muscle growth and production of the other factor. In Crohn's disease, IGF-I and IGFBP-5 expression are increased and contribute to stricture formation through this effect on muscle growth. To determine the signaling pathways coupling IGFBP-5 to MAPK activation and growth, smooth muscle cells were isolated from muscularis propria of human intestine and placed into primary culture. Erk1\/2 and p38 MAPK activation and type I collagen production were measured by immunoblot. Proliferation was measured by [<jats:sup>3<\/jats:sup>H]thymidine incorporation. Activation of specific G proteins was measured by ELISA. AG1024, an IGF-I receptor tyrosine kinase inhibitor, was used to isolate the IGF-I-independent effects of IGFBP-5. IGFBP-5-induced phosphorylation of Erk1\/2 and p38 MAPK and proliferation were abolished by pertussis toxin, implying the participation of Gi. IGFBP-5 specifically activated Gi3 but not other G proteins. Transfection of an inhibitory G\u03b1i minigene specifically inhibited MAPK activation, proliferation, and both collagen-I and IGF-I production. Our results indicate that endogenous IGFBP-5 activates Gi3 and regulates smooth muscle growth, IGF-I production, and collagen production via the \u03b1-subunit of Gi3, independently of IGF-I, in normal human intestinal muscle cells.<\/jats:p>","DOI":"10.1152\/ajpgi.00323.2009","type":"journal-article","created":{"date-parts":[[2009,10,2]],"date-time":"2009-10-02T01:59:37Z","timestamp":1254448777000},"page":"G1232-G1238","source":"Crossref","is-referenced-by-count":16,"title":["Insulin-like growth factor-binding protein-5 stimulates growth of human intestinal muscle cells by activation of G\u03b1i3"],"prefix":"10.1152","volume":"297","author":[{"given":"Robert S.","family":"Flynn","sequence":"first","affiliation":[{"name":"Departments of 1Medicine,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunila","family":"Mahavadi","sequence":"additional","affiliation":[{"name":"Physiology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karnam 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