| First Author | Xu W | Year | 2020 |
| Journal | J Diabetes Investig | Volume | 11 |
| Issue | 2 | Pages | 307-314 |
| PubMed ID | 31368666 | Mgi Jnum | J:298486 |
| Mgi Id | MGI:6480172 | Doi | 10.1111/jdi.13124 |
| Citation | Xu W, et al. (2020) Wingless-type MMTV integration site family member 5a is a key inhibitor of islet stellate cells activation. J Diabetes Investig 11(2):307-314 |
| abstractText | AIMS/INTRODUCTION: Type 2 diabetes mellitus is a chronic metabolic disorder characterized by islet beta-cell dysfunction, which might result from the activation of islet stellate cells (ISCs). Our recent study showed that a specific population of ISCs is prone to be activated in type 2 diabetes mellitus accompanied by reduced secretion of insulin. The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled-5 signaling pathway might play an important role in this process. The present study aimed to explore the effects of Wnt5a on the activation of ISCs isolated from db/db mice. MATERIALS AND METHODS: ISCs were isolated from db/db mice and matched db/m mice. Immunohistochemistry and western blotting analysis were applied for the determination of Wnt5a expression. Exogenous Wnt5a and lentivirus containing the target gene Wnt5a short hairpin ribonucleic acid were used as a molecular intervention. The experiment of transwell and wound healing was used to evaluate the migration of the isolated ISCs. RESULTS: Our data showed that the expression of Wnt5a and frizzled-5 was decreased in the ISCs isolated from db/db mice compared with db/m mice. Both the exogenous Wnt5a and the overexpression of Wnt5a could inhibit the outgrowth rate of ISCs from islets, and its viability, migration and alpha smooth muscle actin expression. These changes were associated with the inactivation of the Smad2/3 signaling pathway in a frizzled-5-dependent manner. CONCLUSIONS: Our observations revealed a potential role of Wnt5a in preventing ISC activation. The maintenance of quiescent ISCs might be a desirable outcome of therapeutic strategies for diabetes mellitus. |
