| First Author | Wang F | Year | 2021 |
| Journal | Hypertension | Volume | 78 |
| Issue | 1 | Pages | 115-127 |
| PubMed ID | 34024121 | Mgi Jnum | J:324586 |
| Mgi Id | MGI:7280815 | Doi | 10.1161/HYPERTENSIONAHA.121.16770 |
| Citation | Wang F, et al. (2021) Mutagenesis of the Cleavage Site of Pro Renin Receptor Abrogates Angiotensin II-Induced Hypertension in Mice. Hypertension 78(1):115-127 |
| abstractText | It is well demonstrated that activation of renal PRR ([pro]renin receptor) contributes to AngII (angiotensin II)-induced hypertension. Relatively, less is known for the function of sPRR (soluble PRR), the extracellular domain of PRR, primarily generated by S1P (site-1 protease) and furin. Moreover, the relationship between PRR/sPRR and the renin-angiotensin system (RAS) has been debated. In the present study, we used CRISPR/Cas9 strategy to generate mice with mutagenesis of the overlapping cleavage site for both proteases in PRR (termed as PRRR279V/L282V) to examine the phenotype during AngII infusion with particular emphasis on circulating and intrarenal renin status. PRRR279V/L282V mice exhibited a reduction of sPRR level in plasma by â53% and in the kidney by â82%, were fertile, and had no gross developmental abnormalities. At basal condition, PRRR279V/L282V mice had drastically suppressed renin levels from plasma, urine, and the kidney as compared to wild- type controls. The hypertensive response of PRRR279V/L282V to AngII infusion was blunted in parallel with attenuated response of intrarenal renin and renal medullary α-epithelial sodium channel expression. By using Ussing chamber technique, primary collecting duct cells from PRRR279V/L282V mice exhibited blunted response of epithelial sodium channel activity to AngII as compared to wild-type cells. Together, these results represent strong evidence favoring sPRR as a mediator of AngII-induced hypertension and a master regulator of renin expression. Therefore, PRR should be considered as an integrative member of the RAS. (Hypertension. 2021;78:115â127. DOI: 10.1161/HYPERTENSIONAHA.121.16770.) |
