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

  • Impact factors: 7
  • Publication: Journal of Animal Science and Biotechnology
  • Author:Ma Xinhao, Yang Xinran, Zhang Dianqi, Zhang Wenzhen, Wang Xiaoyu, Xie Kuncheng, He Jie, Mei Chugang, Zan Linsen
  • DOI citation-doi:10.1186/s40104-022-00820-1
  • Date:2023-02-03T00:00:00.000Z

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.

Related Products

$447.00$569.00

$400.00$500.00

$400.00$500.00

$400.00$500.00

$400.00$500.00

$400.00$500.00

$400.00$500.00

$400.00$500.00

EK1392

$350.00$450.00

EK1242

$350.00$450.00

EK1C01

$350.00$450.00

EK1341

$350.00$450.00

EK1334

$350.00$450.00

EK2295

$350.00$450.00

EK224

$350.00$450.00

EK2100

$350.00$450.00

Hot products

Hot citation