Abstract: SA-PO761
Knockdown of Central (Pro)Renin Receptor Attenuates Renal Injury in a High-Salt-Load CKD Rat Model
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Li, Jiawen, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Li, Aiqing, Nanfang Hospital, Southern Medical University, Guangzhou, China
Background
High-salt promotes renal injury in chronic kidney disease (CKD) through activating the RAS axis of the brain and kidney. Simultaneously, (pro)renin receptor (PRR) can exert local physiological effects in brain.However, the mechanism of central PRR in regulating salt-induced renal injury in CKD remains unclear.Therefore, we investigate the role of central PRR on renal injury in salt-loaded CKD rats in this study.Furthermore, we also investigate the potential mechanism of central PRR ameliorating renal injury.
Methods
Protocol A, First, we screened out the sequences that inhibit the central PRR expression in vitro. After the CKD model, which was established by 5/6 nephrectomy, was successfully prepared, intraventricular injection of lentivirus-packaged shRNA was used and a high-salt diet was given for 4 weeks. Finally, renal pathologic change was detected.
Protocol B, U0126, Wortmannin and Losartan were used to inhibit MAPK/ERK1/2,PI3K/Akt signaling pathway, and ACE1-Ang II-AT1 axis in CKD model by continuous central administration and a high-salt diet was given for 4 weeks, respectively. Finally, we investigated the central and renal pathological changes.
Results
High-salt diet could aggravate kidney damage and fibrosis, increased RAS activation, oxidative stress, and inflammation. After successful inhibition of central PRR expression, the activity of the sympathetic nervous system (SNA) was decreased, kidney damage, renal fibrosis, RAS activation, oxidative stress, and inflammation were diminished. Furthermore, phosphorylation of ERK1/2 and Akt in central were inhibited.
Central administration of U0126, Wortmannin, and Losartan was performed. The results revealed that these interventions ameliorated kidney damage, inflammation, oxidative stress, fibrosis, and SNA. However, decreased phosphorylation of ERK1/2 and Akt signaling in the brain had no significant effect on the expression of PRR, but knocking down PRR can inhibit the phosphorylation of these pathways. It suggested that central PRR may affect renal pathology through these signaling pathways.
Conclusion
Centrally knockdown of PRR expression can ameliorate salt-induced renal damage, as well as reduce RAS activation, inflammation, and oxidative stress, thereby slowing down the progression of CKD. Central PRR may affect renal pathology through the ACE1-Ang II-AT1 axis as well as MAPK/ERK1/2 and PI3K/Akt signaling pathways.
Funding
- Government Support - Non-U.S.