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Molecular Medicine

, Volume 17, Issue 1–2, pp 59–69 | Cite as

Angiotensin-Converting Enzyme (ACE) 2 Overexpression Ameliorates Glomerular Injury in a Rat Model of Diabetic Nephropathy: A Comparison with ACE Inhibition

  • Chun Xi Liu
  • Qin Hu
  • Yan Wang
  • Wei Zhang
  • Zhi Yong Ma
  • Jin Bo Feng
  • Rong Wang
  • Xu Ping Wang
  • Bo Dong
  • Fei Gao
  • Ming Xiang Zhang
  • Yun Zhang
Research Article

Abstract

The reduced expression of angiotensin-converting enzyme (ACE) 2 in the kidneys of animal models and patients with diabetes suggests ACE2 involvement in diabetic nephrology. To explore the renoprotective effects of ACE2 overexpression, ACE inhibition (ACEI) or both on diabetic nephropathy and the potential mechanisms involved, 50 Wistar rats were randomly divided into a normal group that received an injection of sodium citrate buffer and a diabetic model group that received an injection of 60 mg/kg streptozotocin. Eight wks after streptozotocin injection, the diabetic rats were divided into no treatment group, adenoviral (Ad)-ACE2 group, Ad-green flurescent protein (GFP) group, ACEI group receiving benazepril and Ad-ACE2 + ACEI group. Four wks after treatment, physical, biochemical, and renal functional and morphological parameters were measured. An experiment in cultured glomerular mesangial cells was performed to examine the effects of ACE2 on cellular proliferation, oxidative stress and collagen IV synthesis. In comparison with the Ad-GFP group, the Ad-ACE2 group exhibited reduced systolic blood pressure, urinary albumin excretion, creatinine clearance, glomeruli sclerosis index and renal malondialdehyde level; downregulated transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF) and collagen IV protein expression; and increased renal superoxide dismutase activity. Ad-ACE2 and ACEI had similar effects, whereas combined use of Ad-ACE2 and ACEI offered no additional benefits. ACE2transfection attenuated angiotensin (Ang) II-induced glomerular mesangial cell proliferation, oxidative stress and collagen IV protein synthesis. In conclusion, ACE2 exerts a renoprotective effect similar to that of ACEI treatment. Decreased renal Ang II, increased renal Ang-(1, 2, 3, 4, 5, 6, 7) levels, and inhibited oxidative stress were the possible mechanisms involved.

Notes

Acknowledgments

We thank Xiang Ming Liang, MD, Jun Hui Zhen, MD, Zhi Hao Wang, MD, and Zhi Yang, MD, for excellent technical assistance. This work was supported by the National 973 Basic Research Program of China (2009CB521900, 2011CB503906; MX Zhang), the National High-Tech Research and Development Program of China (2006AA02A406; Y Zhang), the Program of Introducing Talents of Discipline to Universities (B07035; Y Zhang), the State Key Program of National Natural Science of China (60831003; Y Zhang), the Cultivation Fund of the Key Scientific and Technical Innovation Project, the Ministry of Education of China (704030; Y Zhang), a grant from the National Natural Science Foundation of China (30670873; Y Zhang) and the Science and Technology Development Program of Shandong Province (2008GGG30002021, Q Hu).

Supplementary material

10020_2011_1701059_MOESM1_ESM.pdf (870 kb)
Supplementary material, approximately 650 KB.

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Chun Xi Liu
    • 1
    • 2
  • Qin Hu
    • 1
  • Yan Wang
    • 1
  • Wei Zhang
    • 1
  • Zhi Yong Ma
    • 1
  • Jin Bo Feng
    • 1
  • Rong Wang
    • 1
  • Xu Ping Wang
    • 1
  • Bo Dong
    • 1
  • Fei Gao
    • 1
  • Ming Xiang Zhang
    • 1
  • Yun Zhang
    • 1
  1. 1.Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of HealthShandong University Qilu HospitalJinan, Shandong, PRChina
  2. 2.Cellular Immunology Laboratory, School of MedicineTsinghua UniversityBeijingChina

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