1. Academic Validation
  2. The protective effect of high mobility group protein HMGA2 in pressure overload-induced cardiac remodeling

The protective effect of high mobility group protein HMGA2 in pressure overload-induced cardiac remodeling

  • J Mol Cell Cardiol. 2019 Mar;128:160-178. doi: 10.1016/j.yjmcc.2019.01.027.
Qing-Qing Wu 1 Yang Xiao 1 Chen Liu 1 Mingxia Duan 1 Zhulan Cai 1 Saiyang Xie 1 Yuan Yuan 1 Haiming Wu 1 Wei Deng 1 Qizhu Tang 2
Affiliations

Affiliations

  • 1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
  • 2 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China. Electronic address: [email protected].
Abstract

High mobility group protein AT-hook 2 (HMGA2), an architectural transcription factor, has previously been reported to play an essential role in regulating the expression of many genes through architectural remodeling processes. However, the effects of HMGA2 on Cardiovascular Disease, especial cardiac remodeling, is unclear. This study was aimed at investigating the functional role of HMGA2 in pressure overload-induced cardiac remodeling. Mice that were subjected to aortic banding (AB) for 8 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with altered expression of HMGA2. Cardiac-specific expression of the human HMGA2 gene in mice with an adeno-related virus 9 delivery system ameliorated cardiac remodeling and improve cardiac function in response to pressure overload by activating PPARγ/NRF2 signaling. Knockdown of HMGA2 by AAV9-shHMGA2 accelerated cardiac remodeling after 1 weeks of AB surgery. Additionally, knockdown of heart PPARγ largely abolished HMGA2 overexpression-mediated cardioprotection. HMGA2-mediated cardiomyocyte protection was largely abrogated by knocking down NRF2 and inhibiting PPARγ in cardiomyocytes. PPARγ activation was mediated by C/EBPβ, which directly interacted with HMGA2. Knocking down C/EBPβ offset the effects of HMGA2 on PPARγ activation and cardioprotection. These findings show that the overexpression of HMGA2 ameliorates the remodeling response to pressure overload, and they also imply that the upregulation of HMGA2 may become a treatment strategy in cardiac pathologies.

Keywords

C/EBPβ; Cardiac remodeling; HMGA2; NRF2; PPARγ.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16578
    99.87%, PPARγ Antagonist