title: Insulin-Like Growth Factor-1 Contributes to Mucosal Repair by β-Arrestin2-Mediated Extracellular Signal-Related Kinase Signaling in Experimental Colitis.
abstract: Insulin-like growth factor-1 (IGF-1) possesses the ability to attenuate intestinal damage and promote mucosal repair of colitis. β-Arrestins, as the scaffolding proteins of G protein-coupled receptors or non-G protein-coupled receptors signaling, can be involved in IGF-1-mediated signaling pathways. However, the interaction of IGF-1 and β-arrestin2 in the mucosal repair of experimental colitis remains unexplored. Ulcerative colitis was induced in β-arrestin2 wild-type mice and β-arrestin2 knockout littermates by using 3% dextran sulfate sodium for 5 days, followed by regular water consumption for 1, 2, 3, and 4 weeks to analyze the mucosal repair from experimental colitis. Disease activity index and histologic score analyses were performed. Apoptosis and proliferation were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Ki-67 staining, respectively. The expressions of β-arrestin2, phospho (p)-IGF-1R, and p-extracellular signal-regulated kinase (ERK)1/2 were examined. Furthermore, β-arrestin2 was overexpressed or altered in HCT116 cells by transfection before IGF-1 treatment in vitro. IGF-1 and β-arrestin2 expression was up-regulated in the repairing phase of experimental colitis. Targeted deletion of β-arrestin2 delayed the repair of colitis by inhibiting cell proliferation without affecting the levels of IGF-1 and p-IGF-1R. The β-arrestin2/ERK signaling pathway was involved in IGF-1-mediated mucosal repair through promoting epithelial cell and goblet cell regeneration from experimental colitis. These results indicate that IGF-1 contributes to the mucosal repair by β-arrestin2-mediated ERK signaling in experimental colitis.
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Lixian
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. Electronic address: wubin6@mail.sysu.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019390:Arrestins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D003092:Colitis / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008810:Mice, Inbred C57BL; D014945:Wound Healing / Q000502:physiology*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D000071557:beta-Arrestins; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D048049:Extracellular Signal-Regulated MAP Kinases