Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival

作     者：Yaoting Deng Yurika Matsui Wenfei Pan Qiu Li Zhi-Chun Lai 

作者机构：Department of Biochemistry and Molecular Biology Pennsylvania State University University Park PA 16802 USA Intercollege Graduate Degree Program in Molecular Cellular and Integrative Biosciences Pennsylvania State University University Park PA 16802 USA Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021 China Department of Biology Pennsylvania State University University Park PA 16802 USA 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2016年第7卷第5期

页      面：362-372页

核心收录：

学科分类：0710[理学-生物学] 0832[工学-食品科学与工程（可授工学、农学学位）] 07[理学] 08[工学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 083203[工学-农产品加工及贮藏工程] 

主　　题：β-cell CTGF F-actin free fatty acid Hipposignaling Yap1 

摘      要：Mammalian pancreatic β-cells play a pivotal role in development and glucose homeostasis through the production and secretion of insulin. Functional failure or decrease in β-cell number leads to type 2 diabetes （T2D）. Despite the physiological importance of β-cells, the viability of β-cells is often challenged mainly due to its poor ability to adapt to their changing microenvironment. One of the factors that negatively affect β-cell viability is high concentration of free fatty acids （FFAs） such as palmitate. In this work, we demonstrated that Yes-associated protein （Yap1） is activated when β-cells are treated with palmitate. Our loss- and gain-of-function analyses using rodent insulinoma cell lines revealed that Yap1 suppresses palmitate-induced apoptosis in β-cells without regulating their proliferation. We also found that upon palmitate treatment, re-arrangement of F-actin mediates Yap1 activation. Palmitate treatment increases expression of one of the Yap1 target genes, connective tissue growth factor （CTGF）. Our gain-offunction analysis with CTGF suggests CTGF may be the downstream factor of Yap1 in the protective mechanism against FFA-induced apoptosis.