title: Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Intercollege Graduate Degree Program in Molecular, Cellular and Integrative Biosciences, Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Pan
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. liqiu10@163.com.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, 16802, USA. zcl1@psu.edu.|Intercollege Graduate Degree Program in Molecular, Cellular and Integrative Biosciences, Pennsylvania State University, University Park, PA, 16802, USA. zcl1@psu.edu.|Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. zcl1@psu.edu.|Department of Biology, Pennsylvania State University, University Park, PA, 16802, USA. zcl1@psu.edu.
authors.forename: Zhi-Chun
authors.initials: ZC
authors.lastname: Lai
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D019308:Palmitic Acid / Q000494:pharmacology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005230:Fatty Acids, Nonesterified; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D053778:Thiazolidines; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D055513:Connective Tissue Growth Factor; D015638:Cytochalasin D; D019308:Palmitic Acid; C037068:latrunculin B
keywords: CTGF; F-actin; Hippo signaling; Yap1; free fatty acid; β-cell