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Kidney Week

Abstract: FR-PO1000

Angiotensin-(1-7) Attenuates Renal Injury in Experimental Alport Syndrome

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Choi, Hong sang, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Kim, Chang Seong, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Ma, Seong Kwon, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Kim, Soo Wan, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Scholey, James W., University of Toronto, Toronto, Ontario, Canada
  • Bae, Eun Hui, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
Background

Angiotensin-(1–7) [Ang-(1–7)] antagonize the actions of the renin-angiotensin-aldosterone system via the Mas receptor and thereby has a renoprotective effects. Previously, murine recombinant angiotensin-converting enzyme (ACE) 2 has been reported to have renoprotective effects in experimental Alport syndrome but the effect of direct administration of Ang-(1-7) has not been studied.

Methods

To examine the effects of Ang-(1-7) on Alport syndrome, Col4a3 knockout mice, a model of Alport syndrome were used. Mice were divided into three groups: saline-treated wild type mice group, saline-treated Col4a3 knockout mice group, and Ang-(1-7) treated Col4a3 knockout mice group. Ang-(1–7) was continuously infused (25 μg/[kg×h]) using osmotic mini-pumps.

Results

Col4a3 knockout mice revealed increased α-smooth muscle actin (SMA) and fibronectin expression which attenuated by Ang-(1-7) treatment. Messenger RNA (mRNA) expression of α-SMA, fibronectin and Collagen I were suppressed by Ang-(1-7) treatment. Ang-(1-7) treatment alleviated the transforming growth factor (TGF)-β/Smad signaling. Ang-(1-7) attenuated protein expression of ED-1 and heme oxygenase-1, indicating the attenuation of renal inflammation. mRNA expression of inflammatory cytokine, TNF-α, MCP-1 and adhesion molecule ICAM-1, VCAM-1 were also decreased by Ang-(1-7) treatment. The ratio of cleaved caspase 3 to caspase 3 was increased in Col4A3 knockout mice kidney which was decreased by ang-(1-7) treatment, indicating attenuation of apoptosis by ang-(1-7). Lastly, ang-(1-7) influenced the alter the ACE2-Ang-(1-7)-Mas receptor axis, as it downregulated angiotensin-1 receptor and upregulated ACE2 and Mas receptor.

Conclusion

Thus, treatment with ang-(1-7) alter the ACE2-Ang-(1-7)-Mas receptor axis in the kidneys of Col4a3 knockout mice and attenuates the progression of Alport syndrome nephropathy.