| First Author | Chen T | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 9 | Pages | 2441-53 |
| PubMed ID | 26362717 | Mgi Jnum | J:227008 |
| Mgi Id | MGI:5699508 | Doi | 10.1016/j.ajpath.2015.05.020 |
| Citation | Chen T, et al. (2015) Insulin-Like Growth Factor-1 Contributes to Mucosal Repair by beta-Arrestin2-Mediated Extracellular Signal-Related Kinase Signaling in Experimental Colitis. Am J Pathol 185(9):2441-53 |
| abstractText | Insulin-like growth factor-1 (IGF-1) possesses the ability to attenuate intestinal damage and promote mucosal repair of colitis. beta-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 beta-arrestin2 in the mucosal repair of experimental colitis remains unexplored. Ulcerative colitis was induced in beta-arrestin2 wild-type mice and beta-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 beta-arrestin2, phospho (p)-IGF-1R, and p-extracellular signal-regulated kinase (ERK)1/2 were examined. Furthermore, beta-arrestin2 was overexpressed or altered in HCT116 cells by transfection before IGF-1 treatment in vitro. IGF-1 and beta-arrestin2 expression was up-regulated in the repairing phase of experimental colitis. Targeted deletion of beta-arrestin2 delayed the repair of colitis by inhibiting cell proliferation without affecting the levels of IGF-1 and p-IGF-1R. The beta-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 beta-arrestin2-mediated ERK signaling in experimental colitis. |
