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miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8

BACKGROUND: Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which can lead to renal failure and fatality. miRNAs are an important class of endogenous non-coding RNAs implicated in a wide range of biological processes and pathological conditions. This study...

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Autores principales: Zhuang, Langen, Ge, Xiaoxu, Hu, Xiaolei, Yang, Qingqing, Pei, Xiaoyan, Jin, Guoxi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895563/
https://www.ncbi.nlm.nih.gov/pubmed/35246069
http://dx.doi.org/10.1186/s12882-022-02716-8
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author Zhuang, Langen
Ge, Xiaoxu
Hu, Xiaolei
Yang, Qingqing
Pei, Xiaoyan
Jin, Guoxi
author_facet Zhuang, Langen
Ge, Xiaoxu
Hu, Xiaolei
Yang, Qingqing
Pei, Xiaoyan
Jin, Guoxi
author_sort Zhuang, Langen
collection PubMed
description BACKGROUND: Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which can lead to renal failure and fatality. miRNAs are an important class of endogenous non-coding RNAs implicated in a wide range of biological processes and pathological conditions. This study aims to investigate the potential functional roles of miR-543 in DN and its underlying mechanisms. METHODS: qRT-PCR was performed to detect the expression levels of miR-543 and TSPAN8 in kidney tissues of mice with DN. Western blot (WB) was used to measure the protein levels. CCK8 assay was employed to evaluate the proliferation of HK2 cells. Dual luciferase reporter assay was conducted to verify the functional interaction between miR-543 and TSpan8. RESULTS: The downregulation of miR-543 and upregulation of TSPAN8 were observed in kidney tissues of mice with DN. miR-543 mimic significantly decreased cell proliferation and autophagy in high-glucose (HG)-induced HK2 cells, and promoted cell fibrosis. We further identified a putative binding site between miR-543 and TSPAN8, which was validated by Dual luciferase reporter assay. The treatment of miR-543 mimic and miR-543 inhibitor could reduce or increase TSPAN8 protein level respectively. We further showed that the overexpression of TSPAN8 could attenuate HG-induced cell injury by reducing fibrosis and increase autophagy. The effects of miR-543 mimic in proliferation, fibrosis, and autophagy were rescued by TSPAN8 overexpression. CONCLUSIONS: Our study indicate that miR-543 mediates high-glucose induced DN via targeting TSPAN8. Interfering miR-543/TSPAN8 axis could serve as potential approach to ameliorate DN. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-022-02716-8.
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spelling pubmed-88955632022-03-10 miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8 Zhuang, Langen Ge, Xiaoxu Hu, Xiaolei Yang, Qingqing Pei, Xiaoyan Jin, Guoxi BMC Nephrol Research BACKGROUND: Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which can lead to renal failure and fatality. miRNAs are an important class of endogenous non-coding RNAs implicated in a wide range of biological processes and pathological conditions. This study aims to investigate the potential functional roles of miR-543 in DN and its underlying mechanisms. METHODS: qRT-PCR was performed to detect the expression levels of miR-543 and TSPAN8 in kidney tissues of mice with DN. Western blot (WB) was used to measure the protein levels. CCK8 assay was employed to evaluate the proliferation of HK2 cells. Dual luciferase reporter assay was conducted to verify the functional interaction between miR-543 and TSpan8. RESULTS: The downregulation of miR-543 and upregulation of TSPAN8 were observed in kidney tissues of mice with DN. miR-543 mimic significantly decreased cell proliferation and autophagy in high-glucose (HG)-induced HK2 cells, and promoted cell fibrosis. We further identified a putative binding site between miR-543 and TSPAN8, which was validated by Dual luciferase reporter assay. The treatment of miR-543 mimic and miR-543 inhibitor could reduce or increase TSPAN8 protein level respectively. We further showed that the overexpression of TSPAN8 could attenuate HG-induced cell injury by reducing fibrosis and increase autophagy. The effects of miR-543 mimic in proliferation, fibrosis, and autophagy were rescued by TSPAN8 overexpression. CONCLUSIONS: Our study indicate that miR-543 mediates high-glucose induced DN via targeting TSPAN8. Interfering miR-543/TSPAN8 axis could serve as potential approach to ameliorate DN. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-022-02716-8. BioMed Central 2022-03-04 /pmc/articles/PMC8895563/ /pubmed/35246069 http://dx.doi.org/10.1186/s12882-022-02716-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhuang, Langen
Ge, Xiaoxu
Hu, Xiaolei
Yang, Qingqing
Pei, Xiaoyan
Jin, Guoxi
miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8
title miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8
title_full miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8
title_fullStr miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8
title_full_unstemmed miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8
title_short miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8
title_sort mir-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting tspan8
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895563/
https://www.ncbi.nlm.nih.gov/pubmed/35246069
http://dx.doi.org/10.1186/s12882-022-02716-8
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