Angiotensin-[1–7] attenuates kidney injury in experimental Alport syndrome

• Published in: Scientific reports 2020-03, Vol.10 (1), p.4225-4225, Article 4225
• Main Authors: Choi, Hong Sang, Kim, In Jin, Kim, Chang Seong, Ma, Seong Kwon, Scholey, James W., Kim, Soo Wan, Bae, Eun Hui
• Format: Article
• Language: English
• Subjects: 631/154/555; 692/4017; ACE2; Actin; Acute Kidney Injury - drug therapy; Acute Kidney Injury - etiology; Acute Kidney Injury - pathology; Alport syndrome; Angiotensin; Angiotensin I - pharmacology; Angiotensin-converting enzyme 2; Animals; Antihypertensive Agents - pharmacology; Apoptosis; Autoantigens - physiology; Cell adhesion molecules; Collagen; Collagen Type IV - physiology; Disease Models, Animal; Enzymes; Fibronectin; Heme; Heme oxygenase (decyclizing); Humanities and Social Sciences; Inflammation; Inflammation - etiology; Inflammation - pathology; Inflammation - prevention & control; Kidneys; Male; Mice; Mice, Knockout; multidisciplinary; Nephritis, Hereditary - complications; Nephritis, Hereditary - pathology; Nephropathy; Oxygenase; Peptide Fragments - pharmacology; Peptidyl-dipeptidase A; Renin; Science; Science (multidisciplinary); Smad protein; Smooth muscle; Transforming growth factor-b; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-61250-5

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 μg/kg/h) using osmotic mini-pumps. Col4a3 −/− mice showed increased α-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-β/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-α 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.