Talin-1 inhibits Smurf1-mediated Stat3 degradation to modulate β-cell proliferation and mass in mice

Hou，Xiaoting1; Chen，Yangshan1; Zhou，Bo1; Tang，Wanze1,2; Ding，Zhen1; Chen，Litong1; Wu，Yun3; Yang，Hongyu3; Du，Changzheng1; Yang，Dazhi2; Ma，Guixing1; Cao，Huiling1

2023-10-01

10.1038/s41419-023-06235-8

Cell Death and Disease   影响因子和分区

2041-4889

2041-4889

Insufficient pancreatic β-cell mass and reduced insulin expression are key events in the pathogenesis of diabetes mellitus (DM). Here we demonstrate the high expression of Talin-1 in β-cells and that deficiency of Talin-1 reduces β-cell proliferation, which leads to reduced β-cell mass and insulin expression, thus causing glucose intolerance without affecting peripheral insulin sensitivity in mice. High-fat diet fed exerbates these phenotypes. Mechanistically, Talin-1 interacts with the E3 ligase smad ubiquitination regulatory factor 1 (Smurf1), which prohibits ubiquitination of the signal transducer and activator of transcription 3 (Stat3) mediated by Smurf1, and ablation of Talin-1 enhances Smurf1-mediated ubiquitination of Stat3, leading to decreased β-cell proliferation and mass. Furthermore, haploinsufficiency of Talin-1 and Stat3 genes, but not that of either gene, in β-cell in mice significantly impairs glucose tolerance and insulin expression, indicating that both factors indeed function in the same genetic pathway. Finally, inducible deletion Talin-1 in β-cell causes glucose intolerance in adult mice. Collectively, our findings reveal that Talin-1 functions as a crucial regulator of β-cell mass, and highlight its potential as a therapeutic target for DM patients.

SCI

英语

第一 ; 通讯

Southern University of Science and Technology["82022047","82372476","81972100"] ; National Natural Science Foundation of China[2019YFA0906001] ; National Key Research and Development Program of China[2017B030301018]

Cell Biology

Cell Biology

WOS:001093774800001

SPRINGERNATURE

2-s2.0-85175330443

Scopus

1.Department of Biochemistry,School of Medicine,Southern University of Science and Technology,Key University Laboratory of Metabolism and Health of Guangdong,Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Southern University of Science and Technology,Shenzhen,518055,China
2.The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,518055,China
3.Department of Oral and Maxillofacial Surgery,Stomatological Center,Peking University Shenzhen Hospital; Guangdong Provincial High-level Clinical Key Specialty; Guangdong Province Engineering Research Center of Oral Disease Diagnosis and Treatment; The Institute of Stomatology,Peking University Shenzhen Hospital,Shenzhen Peking University; The Hong Kong University of Science and Technology Medical Center,Guangdong,China

Hou，Xiaoting,Chen，Yangshan,Zhou，Bo,et al. Talin-1 inhibits Smurf1-mediated Stat3 degradation to modulate β-cell proliferation and mass in mice[J]. Cell Death and Disease,2023,14(10).

Hou，Xiaoting.,Chen，Yangshan.,Zhou，Bo.,Tang，Wanze.,Ding，Zhen.,...&Cao，Huiling.(2023).Talin-1 inhibits Smurf1-mediated Stat3 degradation to modulate β-cell proliferation and mass in mice.Cell Death and Disease,14(10).

Hou，Xiaoting,et al."Talin-1 inhibits Smurf1-mediated Stat3 degradation to modulate β-cell proliferation and mass in mice".Cell Death and Disease 14.10(2023).