| First Author | Choi HS | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 4225 |
| PubMed ID | 32144368 | Mgi Jnum | J:286364 |
| Mgi Id | MGI:6403620 | Doi | 10.1038/s41598-020-61250-5 |
| Citation | Choi HS, et al. (2020) Angiotensin-[1-7] attenuates kidney injury in experimental Alport syndrome. Sci Rep 10(1):4225 |
| abstractText | Angiotensin-[1-7] (Ang-[1-7]) antagonize the actions of the renin-angiotensin-system via the Mas receptor and thereby exert renoprotective effects. Murine recombinant angiotensin-converting enzyme (ACE)2 was reported to show renoprotective effects in an experimental Alport syndrome model; however, the protective effect of direct administration of Ang-[1-7] is unknown. Here, we used Col4a3(-/-) mice as a model of Alport syndrome, which were treated with saline or Ang- [1-7]; saline-treated wild-type mice were used as a control group. The mice were continuously infused with saline or Ang-[1-7] (25 mug/kg/h) using osmotic mini-pumps. Col4a3(-/-) mice showed increased alpha-smooth muscle actin (SMA), collagen, and fibronectin expression levels, which were attenuated by Ang-[1-7] treatment. Moreover, Ang-[1-7] alleviated activation of transforming growth factor-beta/Smad signaling, and attenuated the protein expression of ED-1 and heme oxygenase-1, indicating reduction of renal inflammation. Ang-[1-7] treatment further reduced the expression levels of inflammatory cytokines and adhesion molecules and attenuated apoptosis in human kidney cells. Finally, Ang-[1-7] downregulated TNF-alpha converting enzyme and upregulated ACE2 expression. Thus, treatment with Ang-[1-7] altered the ACE2-Ang-[1-7]-Mas receptor axis in the kidneys of Col4a3(-/-) mice to attenuate the nephropathy progression of Alport syndrome. |
