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<p>Background: Heat shock protein beta 1 (HSPB1) is confirmed to be a ferroptosis-related gene and plays an important role in the progression of diabetic cardiomyopathy (DCM). However, the specific functions and underlying molecular mechanisms of HSPB1 in DCM progression remain to be revealed. Methods: Cardiomyocytes were exposed to high glucose (HG) to mimic DCM cell models. The levels of HSPB1, tripartite motif-containing 55 (TRIM55), upstream stimulating factor 1 (USF1) and fibrosis-related markers were detected using western blot. Cell viability, apoptosis, inflammation, ferroptosis and mitochondrial membrane potential depolarization were assessed by CCK8 assay, flow cytometry, ELISA, corresponding kit and JC-1 staining. The interaction between TRIM55 and HSPB1 or USF1 was confirmed by Co-IP assay, ubiquitination assay, and dual-luciferase reporter assay. Diabetic mouse models were constructed by streptozotocin to assess the role of HSPB1 in vivo. Results: Overexpression of HSPB1 suppressed HG-induced cardiomyocyte apoptosis, ferroptosis, inflammation, mitochondrial dysfunction and fibrosis. TRIM55 enhanced the protein degradation of HSPB1 through ubiquitination, and the inhibitory effect of TRIM55 knockdown on HG-induced cardiomyocyte injury could be reversed by HSPB1 silencing. USF1 bound to TRIM55 promoter to activate its transcription. USF1 knockdown inhibited HG-induced cardiomyocyte injury by mediating the TRIM55/HSPB1 axis. In animal study, HSPB1 overexpression could improve cardiac function, alleviate inflammation and fibrosis in diabetic mouse models. Conclusion: The USF1/TRIM55/HSPB1 axis proposed in this study provides a potential molecular target for the treatment of DCM.</p>

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USF1 transcriptionally activates TRIM55 to promote diabetic cardiomyopathy progression by enhancing HSPB1 protein degradation

  • 期刊论文

  • 发表日期：

    2026年4月10日

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  • Liu Huang,
  • Cheng Zheng,
  • Cuizhu He,
  • Xiang Qiu,
  • Huiqing Wei,
  • Jie Yan,
  • Kun Cui,
  • Wenhui Yang,
  • Lizhuo Yao,
  • Yulian Wei,
  • Xiaohong Nie,
  • Bingyan Guo

摘要

Background: Heat shock protein beta 1 (HSPB1) is confirmed to be a ferroptosis-related gene and plays an important role in the progression of diabetic cardiomyopathy (DCM). However, the specific functions and underlying molecular mechanisms of HSPB1 in DCM progression remain to be revealed. Methods: Cardiomyocytes were exposed to high glucose (HG) to mimic DCM cell models. The levels of HSPB1, tripartite motif-containing 55 (TRIM55), upstream stimulating factor 1 (USF1) and fibrosis-related markers were detected using western blot. Cell viability, apoptosis, inflammation, ferroptosis and mitochondrial membrane potential depolarization were assessed by CCK8 assay, flow cytometry, ELISA, corresponding kit and JC-1 staining. The interaction between TRIM55 and HSPB1 or USF1 was confirmed by Co-IP assay, ubiquitination assay, and dual-luciferase reporter assay. Diabetic mouse models were constructed by streptozotocin to assess the role of HSPB1 in vivo. Results: Overexpression of HSPB1 suppressed HG-induced cardiomyocyte apoptosis, ferroptosis, inflammation, mitochondrial dysfunction and fibrosis. TRIM55 enhanced the protein degradation of HSPB1 through ubiquitination, and the inhibitory effect of TRIM55 knockdown on HG-induced cardiomyocyte injury could be reversed by HSPB1 silencing. USF1 bound to TRIM55 promoter to activate its transcription. USF1 knockdown inhibited HG-induced cardiomyocyte injury by mediating the TRIM55/HSPB1 axis. In animal study, HSPB1 overexpression could improve cardiac function, alleviate inflammation and fibrosis in diabetic mouse models. Conclusion: The USF1/TRIM55/HSPB1 axis proposed in this study provides a potential molecular target for the treatment of DCM.