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

Abstract

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.

• Authors: Hong Sang Choi, In Jin Kim, Chang Seong Kim, Seong Kwon Ma, James W Scholey, Soo Wan Kim, Eun Hui Bae
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 4225 (03 06 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32144368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Autoantigens
• Collagen Type IV
• Peptide Fragments
• type IV collagen alpha3 chain
• Angiotensin I
• angiotensin I (1-7)

Topics

• Acute Kidney Injury (drug therapy, etiology, pathology)
• Angiotensin I (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Apoptosis
• Autoantigens (physiology)
• Collagen Type IV (physiology)
• Disease Models, Animal
• Inflammation (etiology, pathology, prevention & control)
• Male
• Mice
• Mice, Knockout
• Nephritis, Hereditary (complications, pathology)
• Peptide Fragments (pharmacology)