The TRIM21-FOXD1-BCL-2 axis underlies hyperglycaemic cell death and diabetic tissue damage

文献类型： 外文期刊

第一作者： Cheng, Wenwen

作者： Cheng, Wenwen;Cai, Cifeng;Xu, Yifan;Xiao, Xueqi;Shi, Tiantian;Liao, Yueling;Chen, Shasha;Liao, Zhiyong;Wang, Xiaoyi;Zhou, Meiliang

作者机构：

期刊名称：CELL DEATH & DISEASE （ 影响因子：9.0； 五年影响因子：9.2 ）

ISSN： 2041-4889

年卷期： 2023 年 14 卷 12 期

页码：

收录情况： SCI

摘要： Chronic hyperglycaemia is a devastating factor that causes diabetes-induced damage to the retina and kidney. However, the precise mechanism by which hyperglycaemia drives apoptotic cell death is incompletely known. Herein, we found that FOXD1, a FOX family transcription factor specifically expressed in the retina and kidney, regulated the transcription of BCL-2, a master regulator of cell survival. Intriguingly, the protein level of FOXD1, which responded negatively to hyperglycaemic conditions, was controlled by the TRIM21-mediated K48-linked polyubiquitination and subsequent proteasomal degradation. The TRIM21-FOXD1-BCL-2 signalling axis was notably active during diabetes-induced damage to murine retinal and renal tissues. Furthermore, we found that tartary buckwheat flavonoids effectively reversed the downregulation of FOXD1 protein expression and thus restored BCL-2 expression and facilitated the survival of retinal and renal tissues. In summary, we identified a transcription factor responsible for BCL-2 expression, a signalling axis (TRM21-FOXD1-BCL-2) underlying hyperglycaemia-triggered apoptosis, and a potential treatment for deleterious diabetic complications.

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