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Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review
Uncontrolled or chronic hyperglycemia causes kidney failure induced by the dysfunction of biomolecules and upregulation of inflammatory cytokines and growth factors. The reninangiotensin system (RAS) is incorporated in the regulation of renal hemodynamics. In a healthy state, local RAS is independen...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SBDR - Society for Biomedical Diabetes Research
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380095/ https://www.ncbi.nlm.nih.gov/pubmed/34289001 http://dx.doi.org/10.1900/RDS.2021.17.1 |
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author | Bahreini, Elham Rezaei-Chianeh, Yousef Nabi-Afjadi, Mohsen |
author_facet | Bahreini, Elham Rezaei-Chianeh, Yousef Nabi-Afjadi, Mohsen |
author_sort | Bahreini, Elham |
collection | PubMed |
description | Uncontrolled or chronic hyperglycemia causes kidney failure induced by the dysfunction of biomolecules and upregulation of inflammatory cytokines and growth factors. The reninangiotensin system (RAS) is incorporated in the regulation of renal hemodynamics. In a healthy state, local RAS is independent of systemic RAS. However, in pathological conditions such as chronic hyperglycemia, angiotensin II (Ang II) increases locally and causes tissue damage, mainly through the induction of oxidative stress, inflammation, and upregulation of some growth factors and their receptors. Such tissue events may cause disruption of the glomerular filtration barrier, thickening and hypertrophy of the glomerular basement membrane, microvascular hyperpermeability, proteinuria, and finally decrease in the glomerular filtration rate (GFR). Reduced GFR causes the kidney to sense falsely a low blood pressure condition and respond to it by stimulating systemic and local RAS. Therefore, patients with diabetic nephropathy (DN) suffer from chronic hypertension. In contrast to local RAS, there are alternative pathways in the kidney that act protectively by reducing tissue Ang II. Such autoregulatory and protective mechanisms are weakened in chronic kidney disease. Previously, it was presumed that systemic RAS inhibitors such as ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) could prevent renal damage by controlling blood pressure and proteinuria. However, the progression of renal failure to end-stage renal disease (ESRD), despite such treatments, indicates the presence of factors other than Ang II. This review highlights the molecular mechanism in renal disease and discusses pharmaceutical and therapeutic approaches. |
format | Online Article Text |
id | pubmed-9380095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | SBDR - Society for Biomedical Diabetes Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-93800952022-08-30 Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review Bahreini, Elham Rezaei-Chianeh, Yousef Nabi-Afjadi, Mohsen Rev Diabet Stud Review Uncontrolled or chronic hyperglycemia causes kidney failure induced by the dysfunction of biomolecules and upregulation of inflammatory cytokines and growth factors. The reninangiotensin system (RAS) is incorporated in the regulation of renal hemodynamics. In a healthy state, local RAS is independent of systemic RAS. However, in pathological conditions such as chronic hyperglycemia, angiotensin II (Ang II) increases locally and causes tissue damage, mainly through the induction of oxidative stress, inflammation, and upregulation of some growth factors and their receptors. Such tissue events may cause disruption of the glomerular filtration barrier, thickening and hypertrophy of the glomerular basement membrane, microvascular hyperpermeability, proteinuria, and finally decrease in the glomerular filtration rate (GFR). Reduced GFR causes the kidney to sense falsely a low blood pressure condition and respond to it by stimulating systemic and local RAS. Therefore, patients with diabetic nephropathy (DN) suffer from chronic hypertension. In contrast to local RAS, there are alternative pathways in the kidney that act protectively by reducing tissue Ang II. Such autoregulatory and protective mechanisms are weakened in chronic kidney disease. Previously, it was presumed that systemic RAS inhibitors such as ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) could prevent renal damage by controlling blood pressure and proteinuria. However, the progression of renal failure to end-stage renal disease (ESRD), despite such treatments, indicates the presence of factors other than Ang II. This review highlights the molecular mechanism in renal disease and discusses pharmaceutical and therapeutic approaches. SBDR - Society for Biomedical Diabetes Research 2021-08-01 /pmc/articles/PMC9380095/ /pubmed/34289001 http://dx.doi.org/10.1900/RDS.2021.17.1 Text en Copyright © by Lab & Life Press https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 Unported (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Review Bahreini, Elham Rezaei-Chianeh, Yousef Nabi-Afjadi, Mohsen Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review |
title | Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review |
title_full | Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review |
title_fullStr | Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review |
title_full_unstemmed | Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review |
title_short | Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review |
title_sort | molecular mechanisms involved in intrarenal renin-angiotensin and alternative pathways in diabetic nephropathy - a review |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380095/ https://www.ncbi.nlm.nih.gov/pubmed/34289001 http://dx.doi.org/10.1900/RDS.2021.17.1 |
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