Nephrin, a transmembrane protein, is involved in pancreatic beta-cell survival signaling

作者：Kapodistria Katerina; Tsilibary Effie Photini; Politis Panagiotis; Moustardas Petros; Charonis Aristidis; Kitsiou Paraskevi^*

来源：Molecular and Cellular Endocrinology, 2015, 400(C): 112-128.

DOI：10.1016/j.mce.2014.11.003

• Nephrin signaling
• Pancreatic beta-cells
• PI3K-Akt survival signaling
• High glucose
• Nephrin internalization
• Diabetic mouse pancreatic islets

Nephrin, a cell surface signaling receptor, regulates podocyte function in health and disease. We study the role of nephrin in beta-cell survival signaling. We report that in mouse islet beta-cells, and the mouse pancreatic beta-cell line (beta TC-6 cells) nephrin is associated and partly co-localized with PI3-kinase. Incubation of cells with functional anti-nephrin antibodies induced nephrin clustering at the plasma membrane, nephrin phosphorylation and recruitment of PI3-kinase to nephrin thus resulting in increased PI3K-dependent Ala phosphorylation and augmented phosphorylation/inhibition of pro-apoptotic Bad and FoxO. Nephrin silencing abolished Akt activation and increased susceptibility of cells to apoptosis. High glucose impaired nephrin signaling, increased nephrin internalization and up-regulated PKC alpha expression. Interestingly, a marked decrease in nephrin expression and phosphorylated Akt was observed in pancreatic islets of db/db lepr -/- diabetic mice. Our findings revealed that nephrin is involved in beta-cell survival and suggest that glucose-induced changes in nephrin signaling may contribute to gradual pancreatic beta-cell loss in type 2 diabetes.

• 出版日期2015-1-15