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Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury
Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723350/ https://www.ncbi.nlm.nih.gov/pubmed/31390845 http://dx.doi.org/10.3390/biom9080348 |
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author | Ravindran, Sreenithya Pasha, Mazhar Agouni, Abdelali Munusamy, Shankar |
author_facet | Ravindran, Sreenithya Pasha, Mazhar Agouni, Abdelali Munusamy, Shankar |
author_sort | Ravindran, Sreenithya |
collection | PubMed |
description | Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought to play a significant role in the etiology of DN. Microparticles (MPs), the small membrane vesicles containing bioactive signals shed by cells upon activation or during apoptosis, are elevated in diabetes and were identified as biomarkers in DN. However, their exact role in the pathophysiology of DN remains unclear. Here, we examined the effect of MPs shed from renal proximal tubular cells (RPTCs) exposed to high glucose conditions on naïve RPTCs in vitro. Our results showed significant increases in the levels of phosphorylated forms of 4E-binding protein 1 and ERK1/2 (the downstream targets of mTOR and ERK pathways), phosphorylated-eIF2α (an ER stress marker), alpha smooth muscle actin (an EMT marker), and phosphorylated-SMAD2 and nuclear translocation of SMAD4 (markers of TGF-β signaling). Together, our findings indicate that MPs activate key signaling pathways in RPTCs under high glucose conditions. Pharmacological interventions to inhibit shedding of MPs from RPTCs might serve as an effective strategy to prevent the progression of DN. |
format | Online Article Text |
id | pubmed-6723350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67233502019-09-10 Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury Ravindran, Sreenithya Pasha, Mazhar Agouni, Abdelali Munusamy, Shankar Biomolecules Article Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought to play a significant role in the etiology of DN. Microparticles (MPs), the small membrane vesicles containing bioactive signals shed by cells upon activation or during apoptosis, are elevated in diabetes and were identified as biomarkers in DN. However, their exact role in the pathophysiology of DN remains unclear. Here, we examined the effect of MPs shed from renal proximal tubular cells (RPTCs) exposed to high glucose conditions on naïve RPTCs in vitro. Our results showed significant increases in the levels of phosphorylated forms of 4E-binding protein 1 and ERK1/2 (the downstream targets of mTOR and ERK pathways), phosphorylated-eIF2α (an ER stress marker), alpha smooth muscle actin (an EMT marker), and phosphorylated-SMAD2 and nuclear translocation of SMAD4 (markers of TGF-β signaling). Together, our findings indicate that MPs activate key signaling pathways in RPTCs under high glucose conditions. Pharmacological interventions to inhibit shedding of MPs from RPTCs might serve as an effective strategy to prevent the progression of DN. MDPI 2019-08-06 /pmc/articles/PMC6723350/ /pubmed/31390845 http://dx.doi.org/10.3390/biom9080348 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ravindran, Sreenithya Pasha, Mazhar Agouni, Abdelali Munusamy, Shankar Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury |
title | Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury |
title_full | Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury |
title_fullStr | Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury |
title_full_unstemmed | Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury |
title_short | Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury |
title_sort | microparticles as potential mediators of high glucose-induced renal cell injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723350/ https://www.ncbi.nlm.nih.gov/pubmed/31390845 http://dx.doi.org/10.3390/biom9080348 |
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