Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival.
10.1007/s13238-016-0258-5
- Author:
Yaoting DENG
1
;
Yurika MATSUI
2
;
Wenfei PAN
3
;
Qiu LI
4
;
Zhi-Chun LAI
5
Author Information
1. Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, 16802, USA.
2. Intercollege Graduate Degree Program in Molecular, Cellular and Integrative Biosciences, Pennsylvania State University, University Park, PA, 16802, USA.
3. Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
4. Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. liqiu10@163.com.
5. Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, 16802, USA. zcl1@psu.edu.
- Publication Type:Journal Article
- Keywords:
CTGF;
F-actin;
Hippo signaling;
Yap1;
free fatty acid;
β-cell
- MeSH:
Actins;
metabolism;
Adaptor Proteins, Signal Transducing;
antagonists & inhibitors;
genetics;
metabolism;
Animals;
Apoptosis;
drug effects;
physiology;
Bridged Bicyclo Compounds, Heterocyclic;
pharmacology;
Cell Line, Tumor;
Connective Tissue Growth Factor;
genetics;
metabolism;
pharmacology;
Cytochalasin D;
pharmacology;
Fatty Acids, Nonesterified;
pharmacology;
HEK293 Cells;
Humans;
Immunohistochemistry;
Insulin-Secreting Cells;
cytology;
drug effects;
metabolism;
Mice;
Microscopy, Fluorescence;
Palmitic Acid;
pharmacology;
Phosphoproteins;
antagonists & inhibitors;
genetics;
metabolism;
RNA Interference;
RNA, Small Interfering;
metabolism;
Rats;
Recombinant Proteins;
genetics;
metabolism;
pharmacology;
Thiazolidines;
pharmacology
- From:
Protein & Cell
2016;7(5):362-372
- CountryChina
- Language:English
-
Abstract:
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-of-function analysis with CTGF suggests CTGF may be the downstream factor of Yap1 in the protective mechanism against FFA-induced apoptosis.
