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hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes

Apoptosis of podocytes contributes to proteinuria in many chronic kidney diseases. The cytokine, tumor necrosis factor-α (TNF-α) is thought to be involved in podocyte apoptosis, but the underlying mechanism is not understood. In our study, we established a model of TNF-α-induced apoptosis by isolati...

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Autores principales: Zhao, Shili, Feng, Junxia, Wang, Qi, Tian, Lu, Zhang, Yunfang, Li, Hongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997802/
https://www.ncbi.nlm.nih.gov/pubmed/29724888
http://dx.doi.org/10.1042/BSR20180288
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author Zhao, Shili
Feng, Junxia
Wang, Qi
Tian, Lu
Zhang, Yunfang
Li, Hongyan
author_facet Zhao, Shili
Feng, Junxia
Wang, Qi
Tian, Lu
Zhang, Yunfang
Li, Hongyan
author_sort Zhao, Shili
collection PubMed
description Apoptosis of podocytes contributes to proteinuria in many chronic kidney diseases. The cytokine, tumor necrosis factor-α (TNF-α) is thought to be involved in podocyte apoptosis, but the underlying mechanism is not understood. In our study, we established a model of TNF-α-induced apoptosis by isolating primary podocytes from mice. After exposing cells to TNF-α, we determined the expression levels of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and cellular FLICE-inhibitory protein (c-FLIP) and the phosphorylation levels of glycogen synthase kinase β (GSK3β) and extracellular signal-regulated kinase (ERK). We then knocked down or overexpressed the levels of hnRNP K and observed its effects on the expressions of c-FLIP, caspase-8, caspase-3, and the phosphorylation of GSK3β and ERK. In addition, we examined the percentage of cells undergoing apoptosis and studied cell cycle distribution. We found that TNF-α induced apoptosis in podocytes and that the expressions of hnRNP K and c-FLIP were significantly decreased, whereas the phosphorylations of GSK3β and ERK were significantly increased. Both gene knockdown and overexpression of hnRPN K resulted in varied expressions/phosphorylations of c-FLIP, GSK3β, and ERK. Moreover, decreased hnRPN K expression contributed to increased levels of caspase-8 and capase-3, as well as an increase in cell apoptosis and G0/G1 arrest. In conclusion, down-regulated expression of hnRNP K by TNF-α resulted in a decrease in the expression of c-FLIP as well as increases in phosphorylated GSK3β, ERK, caspase-8, and caspase-3, and then critically contributed to the podocyte apoptosis.
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spelling pubmed-59978022018-06-13 hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes Zhao, Shili Feng, Junxia Wang, Qi Tian, Lu Zhang, Yunfang Li, Hongyan Biosci Rep Research Articles Apoptosis of podocytes contributes to proteinuria in many chronic kidney diseases. The cytokine, tumor necrosis factor-α (TNF-α) is thought to be involved in podocyte apoptosis, but the underlying mechanism is not understood. In our study, we established a model of TNF-α-induced apoptosis by isolating primary podocytes from mice. After exposing cells to TNF-α, we determined the expression levels of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and cellular FLICE-inhibitory protein (c-FLIP) and the phosphorylation levels of glycogen synthase kinase β (GSK3β) and extracellular signal-regulated kinase (ERK). We then knocked down or overexpressed the levels of hnRNP K and observed its effects on the expressions of c-FLIP, caspase-8, caspase-3, and the phosphorylation of GSK3β and ERK. In addition, we examined the percentage of cells undergoing apoptosis and studied cell cycle distribution. We found that TNF-α induced apoptosis in podocytes and that the expressions of hnRNP K and c-FLIP were significantly decreased, whereas the phosphorylations of GSK3β and ERK were significantly increased. Both gene knockdown and overexpression of hnRPN K resulted in varied expressions/phosphorylations of c-FLIP, GSK3β, and ERK. Moreover, decreased hnRPN K expression contributed to increased levels of caspase-8 and capase-3, as well as an increase in cell apoptosis and G0/G1 arrest. In conclusion, down-regulated expression of hnRNP K by TNF-α resulted in a decrease in the expression of c-FLIP as well as increases in phosphorylated GSK3β, ERK, caspase-8, and caspase-3, and then critically contributed to the podocyte apoptosis. Portland Press Ltd. 2018-06-12 /pmc/articles/PMC5997802/ /pubmed/29724888 http://dx.doi.org/10.1042/BSR20180288 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Zhao, Shili
Feng, Junxia
Wang, Qi
Tian, Lu
Zhang, Yunfang
Li, Hongyan
hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes
title hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes
title_full hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes
title_fullStr hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes
title_full_unstemmed hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes
title_short hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes
title_sort hnrnp k plays a protective role in tnf-α-induced apoptosis in podocytes
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997802/
https://www.ncbi.nlm.nih.gov/pubmed/29724888
http://dx.doi.org/10.1042/BSR20180288
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