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Abstract: TH-PO867

Effects of Ang-(1-7) and Its Receptor Regulating Bradykinin System on Podocyte Injury Induced by High Glucose

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Chen, Guixiang, Shanghai Ninth People's Hospital, Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, P.R.China., Shanghai, China
  • Shen, Guanghui, Shanghai Ninth People''s Hospital, Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, P.R.China., Shanghai, China
  • Lu, Jianxin, Shanghai Ninth People's Hospital, Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, P.R.China., Shanghai, China
  • Ding, Feng, Shanghai Ninth People's Hospital, Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, P.R.China., Shanghai, China
Background

The mechanisms of diabetic nephropathy are still enigmatic. We hypothesized that RAS component Ang-(1-7) and its Mas receptor (MasR) and bradykinin (BK) system may play a protective role in podocyte injury induced by high glucose.

Methods

The Podocytes cultured in vitro were respectively interfered with low glucose (5mM, LG), high glucose (30mM, HG), HG+Ang-(1-7), HG+HOE140 (BKB2R antagonist), HG+ des[Arg(9)]BK (BKB1R agonist), HG+Ang-(1-7)+A779 [Ang-(1-7) antagonist], HG+ Ang-(1-7)+HOE140 and HG+ Ang-(1-7)+des[Arg(9)]BK. The CCK8 method detected the activity of podocytes and the flow cytometry detected the apoptosis of podocytes. The mRNA and proteinic expression of AT1R, MasR, BKB1R, BKB2R and podocyte-specific proteins (nephrin, podocin, WT-1) was examined by q-PCR and Western blot. The podocytes were also interfered with inhibitor of ERK and JNK, the expression of pERK/ERK, pJNK/JNK in podocytes was semi-quantificated by Western blot to investigate the signaling passway involved in the regulation.

Results

The CCK8 and flow cytometry results showed that the descent of podocyte activity and podocyte apoptosis induced by HG was rescued by Ang-(1-7) and HOE140. The effect presented concentration dependency. des[Arg(9)]BK and A779 displayed antagonistic action against Ang-(1-7), which aggratated the podocyte apoptosis and the descent of cell activity, moreover, the effect was most obviously at 10uM concentration. The results of q-PCR and Western blot indicated that HG stimulation up-regulated the expression of AT1R, BKB1R, BKB2R and down-regulated MasR, Nephrin, Podocin and WT-1. Ang-(1-7) and HOE140 could relieve the action of HG but A779 and des[Arg(9)]BK was the converse of Ang-(1-7) in some extent. The synergetic protective effect of HOE140 and Ang-(1-7) was more significantly. HG and des[Arg (9)]BK activated the MAPKs signaling passway yet Ang-(1-7) and HOE140 inhibited it. The inhibitor of MAPKs further decreased the podocyte apoptosis induced by HG.

Conclusion

Ang-(1-7)/MasR may decrease the up-regulation of BKB1R and BKB2R induced by HG, antagonist Ang II- ACE-AT1R axis, and then inhibit the activation of MAPKs and podocyte apoptosis. The synergistic reaction of Ang-(1-7)/MasR and BK system could protect podocyte from injury induced by HG.

Funding

  • Private Foundation Support