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

Area of Science:

• Cardiology
• Molecular Biology
• Cellular Biology

Background:

• Myocardial ischemia-reperfusion injury (MIRI) is a critical complication following acute myocardial infarction (AMI).
• Growth arrest and DNA damage-inducible gene 45 Gamma (GADD45G) is implicated in MIRI, but its regulatory mechanisms are not fully understood.
• Hypoxia/reoxygenation (H/R) induces cardiomyocyte damage, apoptosis, oxidative stress, and inflammation.

Purpose of the Study:

• To elucidate the role of SP1 and GADD45G in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury.
• To investigate the regulatory relationship between SP1 and GADD45G in the context of MIRI.
• To assess the therapeutic potential of targeting the SP1/GADD45G pathway for MIRI.

Main Methods:

• Utilized H9C2 cell models exposed to hypoxia/reoxygenation (H/R) to mimic MIRI conditions.
• Assessed cell viability, apoptosis, oxidative stress, and inflammatory markers.
• Employed SP1 knockdown and GADD45G deficiency models.
• Investigated SP1 binding to the GADD45G promoter region.
• Validated findings in a rat model of myocardial ischemia-reperfusion (MI/R) injury.

Main Results:

• H/R treatment significantly reduced H9C2 cell viability and increased apoptosis, oxidative stress, and inflammation.
• GADD45G deficiency attenuated H/R-induced H9C2 cell injury.
• SP1 was identified as a transcription factor that directly binds to the GADD45G promoter, enhancing its transcription.
• SP1 knockdown mitigated MI/R-induced pathological damage in rat myocardial tissue by regulating GADD45G.
• SP1 promotes H/R-induced cardiomyocyte injury and MI/R-induced myocardial tissue damage via upregulation of GADD45G.

Conclusions:

• SP1 acts as a key transcription factor that upregulates GADD45G expression.
• The SP1/GADD45G axis exacerbates cardiomyocyte injury and myocardial tissue damage during MIRI.
• Targeting the SP1/GADD45G pathway presents a promising therapeutic strategy for treating MIRI.