HSF1 promotes the viability of islet β-cells via upregulating SIRPα expression

H.-M. Zhang, M. Yang, X.-Y. Zhang, Y. Tang, J.-L. Wu, J. Huang

Department of Endocrinology and Metabolism, the First People’s Hospital of Liangjiang New District, Chongqing, China. 274512483@qq.com

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• Metabolism

OBJECTIVE: Increasing evidence has shown that HSF1 is involved in glycemia regulation, and SIRPα plays a pivotal role in islet β-cell viability. However, it is still unknown whether SIRPα is associated with HSF1 in regulating the cell viability and cell death of islet β-cells.

MATERIALS AND METHODS: Western blot and qPCR were applied to determine protein and mRNA levels of HSF1 and SIRPα. Cell viability and death were investigated by cell counting kit-8 and trypan blue exclusion assay. Meanwhile, cell apoptosis was analyzed by detecting caspase3 activity. Moreover, luciferase reporter assay was applied to explore the mechanism by which HSF1 transcriptionally upregulated SIRPα expression.

RESULTS: Our study reveals that HSF1 expression was lower in islets from T1DM compared to normal mice. We found that overexpression of HSF1 decreased the apoptosis of islet β-cell lines. Moreover, we demonstrated that overexpression of HSF1 decreased the apoptosis of islet β-cells through increasing the expression of SIRPα. In terms of mechanism, luciferase reporter assays showed that HSF1 upregulated SIRPα expression by activating its gene promoter region. The binding site (-1809 to -1795) was required for HSF1-induced increase of SIRPα gene promoter activity.

CONCLUSIONS: These results indicate that the low expression of HSF1/SIRPα may be one of the mechanisms of islet β-cell death and targeting HSF1/SIRPα may be a novel strategy for the treatment of T1DM.

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