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Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells
Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578147/ https://www.ncbi.nlm.nih.gov/pubmed/28805677 http://dx.doi.org/10.3390/ijms18081758 |
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author | Chen, Xiaoming Cobbs, Alyssa George, Jasmine Chima, Ashmeer Tuyishime, Fidele Zhao, Xueying |
author_facet | Chen, Xiaoming Cobbs, Alyssa George, Jasmine Chima, Ashmeer Tuyishime, Fidele Zhao, Xueying |
author_sort | Chen, Xiaoming |
collection | PubMed |
description | Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in diabetic animals and primary cultured rat TECs exposed to exogenous albumin and high glucose. We also used specific inhibitors to determine if internalization of albumin and/or extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were required for MMP-9 secretion. Immunostaining of kidney sections revealed enhanced MMP-9 signal in the damaged proximal tubules in Zucker diabetic fatty (ZDF) rats. ZDF rats also exhibited an albuminuria-related and age-dependent increase in MMP-9 excretion, which was prevented by rosiglitazone. In primary cultured rat TECs, high glucose exposure did not increase MMP-9 secretion. In contrast, administration of rat serum albumin (RSA, 0.1–0.5 mg/mL) resulted in a dose-dependent increase in MMP-9 expression and secretion by TECs, which was abolished in the presence of an ERK1/2-specific inhibitor, U0126. Simvastatin, an inhibitor of albumin endocytosis, also prevented MMP-9 secretion. Taken together, these results demonstrate that endocytosis of albumin stimulates MMP-9 secretion by TECs through the ERK signaling pathway. |
format | Online Article Text |
id | pubmed-5578147 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-55781472017-09-05 Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells Chen, Xiaoming Cobbs, Alyssa George, Jasmine Chima, Ashmeer Tuyishime, Fidele Zhao, Xueying Int J Mol Sci Article Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in diabetic animals and primary cultured rat TECs exposed to exogenous albumin and high glucose. We also used specific inhibitors to determine if internalization of albumin and/or extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were required for MMP-9 secretion. Immunostaining of kidney sections revealed enhanced MMP-9 signal in the damaged proximal tubules in Zucker diabetic fatty (ZDF) rats. ZDF rats also exhibited an albuminuria-related and age-dependent increase in MMP-9 excretion, which was prevented by rosiglitazone. In primary cultured rat TECs, high glucose exposure did not increase MMP-9 secretion. In contrast, administration of rat serum albumin (RSA, 0.1–0.5 mg/mL) resulted in a dose-dependent increase in MMP-9 expression and secretion by TECs, which was abolished in the presence of an ERK1/2-specific inhibitor, U0126. Simvastatin, an inhibitor of albumin endocytosis, also prevented MMP-9 secretion. Taken together, these results demonstrate that endocytosis of albumin stimulates MMP-9 secretion by TECs through the ERK signaling pathway. MDPI 2017-08-12 /pmc/articles/PMC5578147/ /pubmed/28805677 http://dx.doi.org/10.3390/ijms18081758 Text en © 2017 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 Chen, Xiaoming Cobbs, Alyssa George, Jasmine Chima, Ashmeer Tuyishime, Fidele Zhao, Xueying Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells |
title | Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells |
title_full | Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells |
title_fullStr | Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells |
title_full_unstemmed | Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells |
title_short | Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells |
title_sort | endocytosis of albumin induces matrix metalloproteinase-9 by activating the erk signaling pathway in renal tubule epithelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578147/ https://www.ncbi.nlm.nih.gov/pubmed/28805677 http://dx.doi.org/10.3390/ijms18081758 |
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