Abstract: FR-PO681

Estrogen-Related Receptor α (ERRα) Plays Proapoptotic and Proinflammatory Roles in Mesangial Cells

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Gong, Wei, Children's Hospital of Nanjing Medical University, Nanjing, China
  • Zhang, Yue, Children's Hospital of Nanjing Medical University, Nanjing, China
  • Huang, Songming, Children's Hospital of Nanjing Medical University, Nanjing, China
  • Jia, Zhanjun, Children's Hospital of Nanjing Medical University, Nanjing, China
  • Zhang, Aihua, Children's Hospital of Nanjing Medical University, Nanjing, China
Background

Mesangial Cell (MC) apoptosis has been proposed as an important cell clearance mechanism during the uncontrolled MC proliferation. The present study is undertaken to investigate the role of ERRα in MC apoptosis under the normal and pathological conditions.

Methods

The mouse MC line was treated with vehicle or puromycin aminonucleoside (PAN). Then the regulation of ERRα and the role of ERRα in MC apoptosis and inflammation was examined.

Results

PAN induced MC apoptosis by 2.3 folds accompanied by the declined cell viability and enhanced inflammatory response. The apoptosis was further evidenced by the increments of BAX/Bcl-2 ratio and caspase-3 expression. In line with the apoptotic response, we also found a remarkable induction of ERRα, an orphan nuclear receptor, at both mRNA (>5-fold) and protein levels (>2-fold). Interestingly, ERRα silencing by a siRNA approach resulted in an attenuation of MC apoptosis by 45% caused by PAN. Meantime, the inflammatory response was also markedly ameliorated. More importantly, overexpression of ERRα in MCs significantly triggered MC apoptosis in line with increased BAX/Bcl-2 ratio and caspase-3 expression. In PAN-treated MCs, ERRα overexpression further aggravated PAN-induced apoptosis by 2.3-fold.

Conclusion

These data suggested a detrimental effect of ERRα on PAN-induced MC apoptosis and inflammatory response, which could help us to better understand the pathogenic mechanism of MC injury in PAN nephropathy and other glomerular diseases.