Murine recombinant angiotensin-converting enzyme 2 attenuates kidney injury in experimental Alport syndrome

作者：Bae Eun Hui; Fang Fei; Williams Vanessa R^*; Konvalinka Ana; Zhou Xiaohua; Patel Vaibhav B; Song Xuewen; John Rohan; Oudit Gavin Y; Pei York; Scholey James W

来源：Kidney International, 2017, 91(6): 1347-1361.

DOI：10.1016/j.kint.2016.12.022

• Alport syndrome
• angiotensin-converting enzyme 2
• renal fibrosis
• renin-angiotensin system
• TNF alpha-converting enzyme

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase in the renin-angiotensin system that catalyzes the breakdown of angiotensin II to angiotensin 1-7. We have reported that ACE2 expression in the kidney is reduced in experimental Alport syndrome but the impact of this finding on disease progression has not been studied. Accordingly, we evaluated effects of murine recombinant ACE2 treatment in Col4a3 knockout mice, a model of Alport syndrome characterized by proteinuria and progressive renal injury. Murine recombinant ACE2 (0.5 mg/kg/day) was administered from four to seven weeks of age via osmotic mini-pump. Pathological changes were attenuated by murine recombinant ACE2 treatment which ameliorated kidney fibrosis as shown by decreased expression of COL1 alpha 1 mRNA, less accumulation of extracellular matrix proteins, and inhibition of transforming growth factor-beta signaling. Further, increases in proinflammatory cytokine expression, macrophage infiltration, inflammatory signaling pathway activation, and heme oxygenase-1 levels in Col4a3 knockout mice were also reduced by murine recombinant ACE2 treatment. Lastly, murine recombinant ACE2 influenced the turnover of renal ACE2, as it suppressed the expression of tumor necrosis factor-alpha converting enzyme, a negative regulator of ACE2. Thus, treatment with exogenous ACE2 alters angiotensin peptide metabolism in the kidneys of Co14a3 knockout mice and attenuates the progression of Alport syndrome nephropathy.

• 出版日期2017-6
• 单位河北医科大学