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Effects of PPAR-γ in the Myocardium on the Development of Ventricular Septation

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Summary

Ventricular septum defects (VSDs) are common types of congenital heart diseases caused by developmental defect; they contribute to 25%-30% of all adult congenital heart diseases. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is widely expressed in mammalian tissues and in the immune system, regulating cell differentiation and immune and inflammatory responses. The PPAR-γ gene has recently been found crucial for heart development, but the mechanism of action is not clear. This study aims to investigate the effects of the PPAR-γ gene in the myocardium on the development of ventricular septation. In this study, we applied Cre-loxP recombination enzyme (CRE) technology to downregulate the expression of the PPAR-γ gene in different cardiac tissues, RT-PCR to examine the expression of the c-fos and TGF-β1 genes, and histology staining to check the defect of embryonic heart at embryonic day 14.5 (E14.5). We found that the downregulation of the PPAR-γ gene resulted in a ventricular membranous septation defect of the embryonic heart at E14.5. Furthermore, only conversion of a Tnt:Cre, but not Mef2c:Cre, Tie2:Cre, or Wnt:Cre PPAR-γ floxed allele to a null allele resulted in VSD. PPAR-γTnt-Cre/+ embryos showed increases in atrioventricular (AV)-cushion cells and the expression of c-fos gene but no change in the expression of TGF-β1 at E10.5. Our study demonstrates PPAR-γ in the myocardium is required for ventricular septation through regulation of AV-cushion cell proliferation by a Tnt/c-fos signal.

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Acknowledgments

The authors thank Dr. Linglin Xie from the Department of Pathology, University of North Dakota for her free supply of mice.

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Authors and Affiliations

  1. Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Lun Zhou & Ling Tu

  2. Department of Cardiovascular Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Zhao-zhao Wang & Zhi-chao Xiao

Authors
  1. Lun Zhou
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  2. Zhao-zhao Wang
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  3. Zhi-chao Xiao
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  4. Ling Tu
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Corresponding author

Correspondence to Zhi-chao Xiao.

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The authors declare no conflict of interest.

Additional information

This project was supported by Natural Science Foundation of Hubei Province, China (No. 20152015CKB748) and Independent Innovation Foundation of Huazhong University of Science and Technology, China (No. 0118540198).

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Zhou, L., Wang, Zz., Xiao, Zc. et al. Effects of PPAR-γ in the Myocardium on the Development of Ventricular Septation. CURR MED SCI 40, 313–319 (2020). https://doi.org/10.1007/s11596-020-2184-2

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  • DOI: https://doi.org/10.1007/s11596-020-2184-2

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