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PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat
OBJECTIVE: Nephrotoxicity is the main side effect of cyclosporine A and finding an effective combating method is urgent. The present study investigates the improving effect of erythropoietin (EPO) on cyclosporine A induce renal injury in rats and further explores its possible mechanism. METHODS: Rec...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054967/ https://www.ncbi.nlm.nih.gov/pubmed/32090669 http://dx.doi.org/10.1080/0886022X.2020.1729188 |
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author | Liu, Bin Tan, Ping |
author_facet | Liu, Bin Tan, Ping |
author_sort | Liu, Bin |
collection | PubMed |
description | OBJECTIVE: Nephrotoxicity is the main side effect of cyclosporine A and finding an effective combating method is urgent. The present study investigates the improving effect of erythropoietin (EPO) on cyclosporine A induce renal injury in rats and further explores its possible mechanism. METHODS: Recombinant adenovirus for expression of EPO was constructed and injected into kidney with multipoint. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected by kits. HE staining and Masson’s trichrome staining were used to evaluate pathological changes. ELISA was performed to detect the levels of transforming growth factor (TGF)-β1, interleukin (IL)-1β, and IL-6 in serum. Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney were detected according to manufacturer’s instruction. Western blotting was performed to observe the protein expression levels of peroxisome proliferator-activated receptor γ (PPAR γ), Toll-like receptor (TLR) 4, and TGF-β1. RESULTS: Results showed that EPO overexpression in rat kidney could significantly improve renal injury and fibrosis, suppress the release of inflammatory factors and reduce oxidative stress induced by cyclosporine A. Western blotting results showed that EPO overexpression could up-regulate the expression of PPARγ and down-regulate the expression of TLR4 and TGF-β1. Interestingly, when PPARγ activity was inhibited by T0070907, an effective and specific PPARγ inhibitor, the therapeutic effect of EPO was significantly attenuated. CONCLUSION: Taken together, above results shown the protective effect of EPO on cyclosporine A-induced renal injury and confirmed that EPO’s anti-inflammation and antioxidative stress involving the PPAR γ/TLR4/TGFβ1 axis. |
format | Online Article Text |
id | pubmed-7054967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-70549672020-03-12 PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat Liu, Bin Tan, Ping Ren Fail Laboratory Study OBJECTIVE: Nephrotoxicity is the main side effect of cyclosporine A and finding an effective combating method is urgent. The present study investigates the improving effect of erythropoietin (EPO) on cyclosporine A induce renal injury in rats and further explores its possible mechanism. METHODS: Recombinant adenovirus for expression of EPO was constructed and injected into kidney with multipoint. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected by kits. HE staining and Masson’s trichrome staining were used to evaluate pathological changes. ELISA was performed to detect the levels of transforming growth factor (TGF)-β1, interleukin (IL)-1β, and IL-6 in serum. Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney were detected according to manufacturer’s instruction. Western blotting was performed to observe the protein expression levels of peroxisome proliferator-activated receptor γ (PPAR γ), Toll-like receptor (TLR) 4, and TGF-β1. RESULTS: Results showed that EPO overexpression in rat kidney could significantly improve renal injury and fibrosis, suppress the release of inflammatory factors and reduce oxidative stress induced by cyclosporine A. Western blotting results showed that EPO overexpression could up-regulate the expression of PPARγ and down-regulate the expression of TLR4 and TGF-β1. Interestingly, when PPARγ activity was inhibited by T0070907, an effective and specific PPARγ inhibitor, the therapeutic effect of EPO was significantly attenuated. CONCLUSION: Taken together, above results shown the protective effect of EPO on cyclosporine A-induced renal injury and confirmed that EPO’s anti-inflammation and antioxidative stress involving the PPAR γ/TLR4/TGFβ1 axis. Taylor & Francis 2020-02-24 /pmc/articles/PMC7054967/ /pubmed/32090669 http://dx.doi.org/10.1080/0886022X.2020.1729188 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Laboratory Study Liu, Bin Tan, Ping PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat |
title | PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat |
title_full | PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat |
title_fullStr | PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat |
title_full_unstemmed | PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat |
title_short | PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat |
title_sort | ppar γ/tlr4/tgf-β1 axis mediates the protection effect of erythropoietin on cyclosporin a-induced chronic nephropathy in rat |
topic | Laboratory Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054967/ https://www.ncbi.nlm.nih.gov/pubmed/32090669 http://dx.doi.org/10.1080/0886022X.2020.1729188 |
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