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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2016-03-01
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| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1007/s13238-016-0258-5 |
| _version_ | 1797726380019941376 |
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| author | Yaoting Deng Yurika Matsui Wenfei Pan Qiu Li Zhi-Chun Lai |
| author_facet | Yaoting Deng Yurika Matsui Wenfei Pan Qiu Li Zhi-Chun Lai |
| author_sort | Yaoting Deng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T10:44:45Z |
| format | Article |
| id | doaj.art-8ff235ef00ae4a7785d014e85aac88c9 |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T10:44:45Z |
| publishDate | 2016-03-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Protein & Cell |
| spelling | doaj.art-8ff235ef00ae4a7785d014e85aac88c92023-09-02T07:42:46ZengOxford University PressProtein & Cell1674-800X1674-80182016-03-017536237210.1007/s13238-016-0258-5Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survivalYaoting Deng0Yurika Matsui1Wenfei Pan2Qiu Li3Zhi-Chun Lai4Department of Biochemistry and Molecular Biology, Pennsylvania State UniversityIntercollege Graduate Degree Program in Molecular, Cellular and Integrative Biosciences, Pennsylvania State UniversityShandong Provincial Hospital Affiliated to Shandong UniversityShandong Provincial Hospital Affiliated to Shandong UniversityDepartment of Biochemistry and Molecular Biology, Pennsylvania State UniversityABSTRACT 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.http://link.springer.com/article/10.1007/s13238-016-0258-5β-cellCTGFF-actinfree fatty acidHippo signalingYap1 |
| spellingShingle | Yaoting Deng Yurika Matsui Wenfei Pan Qiu Li Zhi-Chun Lai Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival Protein & Cell β-cell CTGF F-actin free fatty acid Hippo signaling Yap1 |
| title | Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival |
| title_full | Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival |
| title_fullStr | Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival |
| title_full_unstemmed | Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival |
| title_short | Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival |
| title_sort | yap1 plays a protective role in suppressing free fatty acid induced apoptosis and promoting beta cell survival |
| topic | β-cell CTGF F-actin free fatty acid Hippo signaling Yap1 |
| url | http://link.springer.com/article/10.1007/s13238-016-0258-5 |
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