Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy
Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and...
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| Format: | Article |
| Language: | English |
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De Gruyter
2016-12-01
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| Series: | Biomolecular Concepts |
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| Online Access: | https://doi.org/10.1515/bmc-2016-0021 |
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| author | Kumar Pasupulati Anil Chitra P. Swathi Reddy G. Bhanuprakash |
| author_facet | Kumar Pasupulati Anil Chitra P. Swathi Reddy G. Bhanuprakash |
| author_sort | Kumar Pasupulati Anil |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff’s base and an Amadori product to yield advanced glycation end products (AGEs). AGE modification of client proteins from the extracellular matrix induces crosslinking, which is often associated with thickening of the basement membrane. AGEs activate several intracellular signaling cascades upon interaction with receptor for AGEs (RAGE), which manifest in aberrant cellular responses such as inflammation, apoptosis and autophagy, whereas other receptors such as AGE-R1, AGE-R3 and scavenger receptors also bind to AGEs and ensue endocytosis and degradation of AGEs. Elevated levels of both serum and tissue AGEs are associated with adverse renal outcome. Increased evidence supports that attenuation of AGE formation and/or inhibition of RAGE activation manifest(s) in improving renal function. This review provides insights of NEG, discusses the cellular and molecular events triggered by AGEs, which manifest in the pathogenesis of DN including renal fibrosis, podocyte epithelial-mesenchymal transition and activation of renin-angiotensin system. Therapies designed to target AGEs, such as inhibitors of AGEs formation and crosslink breakers, are discussed. |
| first_indexed | 2024-12-17T07:07:11Z |
| format | Article |
| id | doaj.art-bb8d5f0a47c44a11849b45785de45d02 |
| institution | Directory Open Access Journal |
| issn | 1868-5021 1868-503X |
| language | English |
| last_indexed | 2024-12-17T07:07:11Z |
| publishDate | 2016-12-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Biomolecular Concepts |
| spelling | doaj.art-bb8d5f0a47c44a11849b45785de45d022022-12-21T21:59:08ZengDe GruyterBiomolecular Concepts1868-50211868-503X2016-12-0175-629330910.1515/bmc-2016-0021Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathyKumar Pasupulati Anil0Chitra P. Swathi1Reddy G. Bhanuprakash2Department of Biochemistry, University of Hyderabad, Hyderabad 500 046, IndiaDepartment of Biochemistry, National Institute of Nutrition, Tarnaka, Hyderabad 500 007, IndiaDepartment of Biochemistry, National Institute of Nutrition, Tarnaka, Hyderabad 500 007, IndiaDiabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff’s base and an Amadori product to yield advanced glycation end products (AGEs). AGE modification of client proteins from the extracellular matrix induces crosslinking, which is often associated with thickening of the basement membrane. AGEs activate several intracellular signaling cascades upon interaction with receptor for AGEs (RAGE), which manifest in aberrant cellular responses such as inflammation, apoptosis and autophagy, whereas other receptors such as AGE-R1, AGE-R3 and scavenger receptors also bind to AGEs and ensue endocytosis and degradation of AGEs. Elevated levels of both serum and tissue AGEs are associated with adverse renal outcome. Increased evidence supports that attenuation of AGE formation and/or inhibition of RAGE activation manifest(s) in improving renal function. This review provides insights of NEG, discusses the cellular and molecular events triggered by AGEs, which manifest in the pathogenesis of DN including renal fibrosis, podocyte epithelial-mesenchymal transition and activation of renin-angiotensin system. Therapies designed to target AGEs, such as inhibitors of AGEs formation and crosslink breakers, are discussed.https://doi.org/10.1515/bmc-2016-0021agesanti-glycating agentsdiabetic nephropathyfibrosisnon-enzymatic glycation |
| spellingShingle | Kumar Pasupulati Anil Chitra P. Swathi Reddy G. Bhanuprakash Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy Biomolecular Concepts ages anti-glycating agents diabetic nephropathy fibrosis non-enzymatic glycation |
| title | Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy |
| title_full | Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy |
| title_fullStr | Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy |
| title_full_unstemmed | Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy |
| title_short | Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy |
| title_sort | advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy |
| topic | ages anti-glycating agents diabetic nephropathy fibrosis non-enzymatic glycation |
| url | https://doi.org/10.1515/bmc-2016-0021 |
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