2. Academic Validation
  3. Transcription Factor SP1 Drives Myocardial Ischemia/reperfusion Injury By Transcription Activation-mediated GADD45G Upregulation

Transcription Factor SP1 Drives Myocardial Ischemia/reperfusion Injury By Transcription Activation-mediated GADD45G Upregulation

  • J Cardiovasc Transl Res. 2026 Feb 5;19(1):19. doi: 10.1007/s12265-025-10739-3.
Yaping Wang 1,  Jianying Xue 1,  Mingliang Cui 1,  Fengjun Chang 1,  Jiankuan Shi 2
Affiliations

Affiliations

  • 1 Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
  • 2 Department of Neurology, Xi'an International Medical Center Hospital, No. 777, Xitai Road, Xi'an, 710100, China. [email protected].
PMID: 41644776 DOI: 10.1007/s12265-025-10739-3
Abstract

Myocardial ischemia-reperfusion injury (MIRI) is an unresolved clinically fatal complication in the management of acute myocardial infarction (AMI). Growth arrest and DNA damage-inducible gene 45 Gamma (GADD45G) plays a vital role in the regulation of MIRI. However, the underlying mechanisms remain unclear. GADD45G and SP1 expression were upregulated in hypoxia/reoxygenation (H/R)-treated H9C2 cells. H/R treatment repressed H9C2 cell viability, and induced Apoptosis, oxidative stress, and inflammatory response. Moreover, GADD45G deficiency could relieve H/R-triggered H9C2 cell injury. In mechanism, SP1 was a transcription factor of GADD45G and activated the transcription of GADD45G via binding to its promoter region. Besides, SP1 knockdown alleviated MI/R-induced pathological damage in the myocardial tissue of rats by regulating GADD45G. In conclusion, SP1 could promote H/R-induced cardiomyocyte injury and MI/R-caused rat myocardial tissue pathological injury by increasing GADD45G, providing a promising therapeutic target for MIRI treatment.

Keywords

GADD45G; H9C2 cardiomyocytes; Inflammatory response; Myocardial ischemia–reperfusion injury; Oxidative stress; SP1.

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