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