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Role of the Renin-Angiotensin System in Diabetic nephropathy
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Mostafa Moazamfard   , Farzaneh Karimi |
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Abstract: (274 Views) |
Introduction: Diabetic nephropathy (DN) is one of the main causes of end-stage renal disease and high mortality rate in type 1 and 2 diabetic patients (T1D and T2D). The RAS plays a pivotal role in the onset and progression of DN.
Search Method: PubMed, Google Scholar, and WOS databases were searched for the effects and interactions of RAS activities during DN with using key words; "renin angiotensin system", "diabetic nephropathy", "angiotensin", "angiotensin II type 1 receptor (AT1R)", and "MasR".
Results: RAS activation plays an important role, being present in the early stages of DN and then being exacerbated by albumin leakage from glomerular capillaries, over production of mesangial cell matrix, podocyte injury and proximal tubular injury. Therefore, activated RAS markers might be useful biomarkers for the diagnosis or monitoring of DN. Urinary angiotensinogen (uAGT) is a marker or tubular injuries of the early stage of DN in T2D. The uAGT excretion is highly correlated with intrarenal Ang II activity and microalbumin, and could serve as a reliable biomarker for monitoring intrarenal RAS status in DN. The ACE2 mRNA expression is decreased in glomeruli and proximal tubules of DN. The rise Ang II levels in DN activates immune cells and causes production of chemokines leading to further renal damage. The AT2R and AT1R expression is decreased in DN. The role of renal RAS inhibitors, like angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and renin inhibitors, have been shown to be an effective reno-protective agent in DN. While genetic deletion of the MasR leads to metabolic syndrome and renal injury, Ang 1–7 activates signaling pathways in mesangial and proximal tubular cells and attenuates DN in Zucker diabetic fatty rats.
Conclusion: the ACE2/ANG 1–7/MasR axis and ACE-I and ARB represents a promising therapeutic approach to the treatment of DN.
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| Keywords: Diabetic nephropathy, Angiotensin II, AT1R, MasR, Renin angiotensin system |
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Full-Text [PDF 317 kb]
(48 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/12/4 | Accepted: 2023/08/23 | Published: 2023/08/23
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