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Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes

BACKGROUND: Palmitate, a common saturated free fatty acid, is increased in patients with diabetic nephropathy (DN). Excessive palmitate in kidney is known to cause proteinuria and fibrosis. Several studies have demonstrated that paclitaxel has anti-fibrotic and anti-inflammatory effects on kidney di...

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Autores principales: Son, Seung Seob, Kang, Jeong Suk, Lee, Eun Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751256/
https://www.ncbi.nlm.nih.gov/pubmed/33323915
http://dx.doi.org/10.12659/MSMBR.928265
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author Son, Seung Seob
Kang, Jeong Suk
Lee, Eun Young
author_facet Son, Seung Seob
Kang, Jeong Suk
Lee, Eun Young
author_sort Son, Seung Seob
collection PubMed
description BACKGROUND: Palmitate, a common saturated free fatty acid, is increased in patients with diabetic nephropathy (DN). Excessive palmitate in kidney is known to cause proteinuria and fibrosis. Several studies have demonstrated that paclitaxel has anti-fibrotic and anti-inflammatory effects on kidney disease. However, whether paclitaxel can relieve podocyte injury is unclear. MATERIAL/METHODS: Immortalized mouse podocytes were used as an in vitro system. Palmitate was used to induce podocyte injury. Podocytes were divided into 4 groups: bovine serum albumin, palmitate, palmitate+1 nM paclitaxel, and palmitate+5 nM paclitaxel. The effects of paclitaxel on palmitate-induced podocyte injury were analyzed by western blot and real-time PCR. Intracellular reactive oxygen species (ROS) generation and podocyte cytoskeletons were analyzed using CM-H2DCF-DA and phalloidin staining. RESULTS: Paclitaxel restored downregulated expression of nephrin and synaptopodin and upregulated VEGF expression after injury induced by palmitate. Remarkably, palmitate-induced actin cytoskeleton rearrangement in podocytes was repaired by paclitaxel. Four endoplasmic reticulum stress markers, ATF-6α, Bip, CHOP, and spliced xBP1, were significantly increased in palmitate-treated podocytes compared with control podocytes. Such increases were decreased by paclitaxel treatment. Palmitate-induced ROS generation was ameliorated by paclitaxel. Elevated Nox4 expression was also improved by paclitaxel. Paclitaxel alleviated the expression levels of the antioxidant molecules, Nrf-2, HO-1, SOD-1, and SOD-2. The paclitaxel effects were accompanied by inhibition of the inflammatory cytokines, MCP-1, TNF-α, TNF-R2, and TLR4, as well as attenuation of the apoptosis markers, Bax, Bcl-2, and Caspase-3. Furthermore, paclitaxel suppressed the palmitate-induced fibrosis molecules, fibronectin and TGF-β1. CONCLUSIONS: This study suggests that paclitaxel could be a therapeutic agent for treating palmitate-induced podocyte injury in DN.
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spelling pubmed-77512562020-12-29 Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes Son, Seung Seob Kang, Jeong Suk Lee, Eun Young Med Sci Monit Basic Res Laboratory Research BACKGROUND: Palmitate, a common saturated free fatty acid, is increased in patients with diabetic nephropathy (DN). Excessive palmitate in kidney is known to cause proteinuria and fibrosis. Several studies have demonstrated that paclitaxel has anti-fibrotic and anti-inflammatory effects on kidney disease. However, whether paclitaxel can relieve podocyte injury is unclear. MATERIAL/METHODS: Immortalized mouse podocytes were used as an in vitro system. Palmitate was used to induce podocyte injury. Podocytes were divided into 4 groups: bovine serum albumin, palmitate, palmitate+1 nM paclitaxel, and palmitate+5 nM paclitaxel. The effects of paclitaxel on palmitate-induced podocyte injury were analyzed by western blot and real-time PCR. Intracellular reactive oxygen species (ROS) generation and podocyte cytoskeletons were analyzed using CM-H2DCF-DA and phalloidin staining. RESULTS: Paclitaxel restored downregulated expression of nephrin and synaptopodin and upregulated VEGF expression after injury induced by palmitate. Remarkably, palmitate-induced actin cytoskeleton rearrangement in podocytes was repaired by paclitaxel. Four endoplasmic reticulum stress markers, ATF-6α, Bip, CHOP, and spliced xBP1, were significantly increased in palmitate-treated podocytes compared with control podocytes. Such increases were decreased by paclitaxel treatment. Palmitate-induced ROS generation was ameliorated by paclitaxel. Elevated Nox4 expression was also improved by paclitaxel. Paclitaxel alleviated the expression levels of the antioxidant molecules, Nrf-2, HO-1, SOD-1, and SOD-2. The paclitaxel effects were accompanied by inhibition of the inflammatory cytokines, MCP-1, TNF-α, TNF-R2, and TLR4, as well as attenuation of the apoptosis markers, Bax, Bcl-2, and Caspase-3. Furthermore, paclitaxel suppressed the palmitate-induced fibrosis molecules, fibronectin and TGF-β1. CONCLUSIONS: This study suggests that paclitaxel could be a therapeutic agent for treating palmitate-induced podocyte injury in DN. International Scientific Literature, Inc. 2020-12-16 /pmc/articles/PMC7751256/ /pubmed/33323915 http://dx.doi.org/10.12659/MSMBR.928265 Text en © Med Sci Monit, 2020 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Laboratory Research
Son, Seung Seob
Kang, Jeong Suk
Lee, Eun Young
Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes
title Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes
title_full Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes
title_fullStr Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes
title_full_unstemmed Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes
title_short Paclitaxel Ameliorates Palmitate-Induced Injury in Mouse Podocytes
title_sort paclitaxel ameliorates palmitate-induced injury in mouse podocytes
topic Laboratory Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751256/
https://www.ncbi.nlm.nih.gov/pubmed/33323915
http://dx.doi.org/10.12659/MSMBR.928265
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