title: Ron receptor signaling is protective against DSS-induced colitis in mice.
abstract: Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the intestine that result in painful and debilitating complications. Currently no cure exists for IBD, and treatments are primarily aimed at reducing inflammation to alleviate symptoms. Genome-wide linkage studies have identified the Ron receptor tyrosine kinase (TK) and its ligand, hepatocyte growth factor-like protein (HGFL), as genes highly associated with IBD. However, only scant information exists on the role of Ron or HGFL in IBD. Based on the linkage of Ron to IBD, we directly examined the biological role of Ron in colitis. Wild-type mice and mice lacking the TK signaling domain of Ron (TK-/- mice) were utilized in a well-characterized model of chronic colitis induced by cyclic exposure to dextran sulfate sodium. In this model, TK-/- mice were more susceptible to injury as judged by increased mortality compared with control mice and developed more severe colitis. Loss of Ron led to significantly reduced body weights and more aggressive clinical and histopathologies. Ron loss also resulted in a dramatic reduction in colonic epithelial cell proliferation and increased proinflammatory cytokine production, which was associated with alterations in important signaling pathways known to regulate IBD. Examination of human gene expression data further supports the contention that loss of Ron signaling is associated with IBD. In total, our studies point to important functional roles for Ron in IBD by regulating healing of the colonic epithelium and by controlling cytokine secretion.
authors.affiliation: Department of Cancer Biology, University of Cincinnati, Cincinnati, Ohio; and.
authors.forename: Rishikesh M
authors.initials: RM
authors.lastname: Kulkarni
authors.affiliation: Department of Cancer Biology, University of Cincinnati, Cincinnati, Ohio; and.
authors.forename: William D
authors.initials: WD
authors.lastname: Stuart
authors.affiliation: Department of Cancer Biology, University of Cincinnati, Cincinnati, Ohio; and.
authors.forename: Devikala
authors.initials: D
authors.lastname: Gurusamy
authors.affiliation: Department of Cancer Biology, University of Cincinnati, Cincinnati, Ohio; and Department of Research, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio susan.waltz@uc.edu.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waltz
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016264:Dextran Sulfate; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases
keywords: Met receptor; Ron receptor; colitis; hepatocyte growth factor-like protein; inflammatory bowel disease
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