| 题名 | Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice |
| 作者 | |
| 通讯作者 | Xiao，Guozhi |
| 发表日期 | 2020-12-01
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| DOI | |
| 发表期刊 | |
| ISSN | 2041-1723
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| EISSN | 2041-1723
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| 卷号 | 11期号:1 |
| 摘要 | β-Cell dysfunction and reduction in β-cell mass are hallmark events of diabetes mellitus. Here we show that β-cells express abundant Kindlin-2 and deleting its expression causes severe diabetes-like phenotypes without markedly causing peripheral insulin resistance. Kindlin-2, through its C-terminal region, binds to and stabilizes MafA, which activates insulin expression. Kindlin-2 loss impairs insulin secretion in primary human and mouse islets in vitro and in mice by reducing, at least in part, Ca release in β-cells. Kindlin-2 loss activates GSK-3β and downregulates β-catenin, leading to reduced β-cell proliferation and mass. Kindlin-2 loss reduces the percentage of β-cells and concomitantly increases that of α-cells during early pancreatic development. Genetic activation of β-catenin in β-cells restores the diabetes-like phenotypes induced by Kindlin-2 loss. Finally, the inducible deletion of β-cell Kindlin-2 causes diabetic phenotypes in adult mice. Collectively, our results establish an important function of Kindlin-2 and provide a potential therapeutic target for diabetes. |
| 相关链接 | [Scopus记录] |
| 收录类别 | |
| 语种 | 英语
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| 重要成果 | NI期刊
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| 学校署名 | 通讯
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| 资助项目 | National Natural Science Foundation of China[81991513][81630066][81870532][81972100]
; National Institutes of Health[AR068950]
; Guangdong Provincial Science and Technology Innovation Council[2017B030301018]
; Shenzhen Municipal Science and Technology Innovation Council[KQJSCX20180319114434843][JCYJ20180302174117738][JCYJ20180302174246105][JSGG20180503182321166][JCYJ20150331101823686][JCYJ20150831142427959]
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| WOS研究方向 | Science & Technology - Other Topics
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| WOS类目 | Multidisciplinary Sciences
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| WOS记录号 | WOS:000543967000007
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| 出版者 | |
| Scopus记录号 | 2-s2.0-85078226134
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| 来源库 | Scopus
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| 引用统计 |
被引频次[WOS]：35
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| 成果类型 | 期刊论文 |
| 条目标识符 | http://sustech.caswiz.com/handle/2SGJ60CL/66972 |
| 专题 | 生命科学学院_生物系 生命科学学院 南方科技大学医学院 |
| 作者单位 | 1.Department of Orthopedic Surgery,Rush University Medical Center,Chicago,60612,United States 2.Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Shenzhen Key Laboratory of Cell Microenvironment,and Department of Biology,Southern University of Science and Technology,Shenzhen,518055,China 3.Department of Cell Biology,School of Basic Medical Sciences,Southern Medical University,Guangzhou,510515,China 4.Department of Orthopedic Surgery,New York University School of Medicine,New York,10003,United States 5.Department of Cell Biology,New York University School of Medicine,New York,10016,United States 6.Department of Molecular Biophysics and Physiology,Rush University Medical Center,Chicago,60612,United States 7.State Key Laboratory of Medicinal Chemical Biology and Nankai University College of Pharmacy,Tianjin,300071,China 8.State Key Laboratory of Experimental Hematology,Institute of Hematology and Blood Disease Hospital,Center for Stem Cell Medicine,Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin,300020,China 9.UVA Islet Microfluidic Laboratory,Department of Surgery,the University of Virginia,Charlottesville,22908,United States 10.Department of Pathology,University of Pittsburgh,Pittsburgh,15261,United States 11.Department of Orthopedic Surgery,Rush University Medical Center,Chicago,60612,United States |
| 通讯作者单位 | 生物系; 南方科技大学医学院; 生命科学学院 |
| 推荐引用方式 GB/T 7714 |
Zhu，Ke,Lai，Yumei,Cao，Huiling,et al. Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice[J]. Nature Communications,2020,11(1).
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| APA |
Zhu，Ke.,Lai，Yumei.,Cao，Huiling.,Bai，Xiaochun.,Liu，Chuanju.,...&Xiao，Guozhi.(2020).Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice.Nature Communications,11(1).
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| MLA |
Zhu，Ke,et al."Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice".Nature Communications 11.1(2020).
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