Cargando…

Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy

Mesangial cell (MC) proliferation and matrix expansion are basic pathological characteristics of IgA nephropathy (IgAN). However, the stepwise mechanism of MC proliferation and the exact set of related signaling molecules remain largely unclear. In this study, we found a significant upregulation of...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Yan, Xia, Ming, Peng, Liang, Liu, Haiyang, Chen, Guochun, Wang, Chang, Yuan, Du, Liu, Yu, Liu, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416718/
https://www.ncbi.nlm.nih.gov/pubmed/34512151
http://dx.doi.org/10.7150/ijbs.61274
_version_ 1783748245331116032
author Li, Yan
Xia, Ming
Peng, Liang
Liu, Haiyang
Chen, Guochun
Wang, Chang
Yuan, Du
Liu, Yu
Liu, Hong
author_facet Li, Yan
Xia, Ming
Peng, Liang
Liu, Haiyang
Chen, Guochun
Wang, Chang
Yuan, Du
Liu, Yu
Liu, Hong
author_sort Li, Yan
collection PubMed
description Mesangial cell (MC) proliferation and matrix expansion are basic pathological characteristics of IgA nephropathy (IgAN). However, the stepwise mechanism of MC proliferation and the exact set of related signaling molecules remain largely unclear. In this study, we found a significant upregulation of miR-214-3p in the renal cortex of IgAN mice by miRNA sequencing. In situ hybridization analysis showed that miR-214-3p expression was obviously elevated in MCs in the renal cortex in IgAN. Functionally, knockdown of miR-214-3p alleviated mesangial hypercellularity and renal lesions in IgAN mice. In vitro, the inhibition of miR-214-3p suppressed MC proliferation and arrested G1-S cell cycle pSrogression in IgAN. Mechanistically, a luciferase reporter assay verified PTEN as a direct target of miR-214-3p. Downregulation of miR-214-3p increased PTEN expression and reduced p-JNK and p-c-Jun levels, thereby inhibiting MC proliferation and ameliorating renal lesions in IgAN. Moreover, these changes could be attenuated by co-transfection with PTEN siRNA. Collectively, these results illustrated that miR-214-3p accelerated MC proliferation in IgAN by directly targeting PTEN to modulate JNK/c-Jun signaling. Therefore, miR-214-3p may represent a novel therapeutic target for IgAN.
format Online
Article
Text
id pubmed-8416718
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-84167182021-09-09 Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy Li, Yan Xia, Ming Peng, Liang Liu, Haiyang Chen, Guochun Wang, Chang Yuan, Du Liu, Yu Liu, Hong Int J Biol Sci Research Paper Mesangial cell (MC) proliferation and matrix expansion are basic pathological characteristics of IgA nephropathy (IgAN). However, the stepwise mechanism of MC proliferation and the exact set of related signaling molecules remain largely unclear. In this study, we found a significant upregulation of miR-214-3p in the renal cortex of IgAN mice by miRNA sequencing. In situ hybridization analysis showed that miR-214-3p expression was obviously elevated in MCs in the renal cortex in IgAN. Functionally, knockdown of miR-214-3p alleviated mesangial hypercellularity and renal lesions in IgAN mice. In vitro, the inhibition of miR-214-3p suppressed MC proliferation and arrested G1-S cell cycle pSrogression in IgAN. Mechanistically, a luciferase reporter assay verified PTEN as a direct target of miR-214-3p. Downregulation of miR-214-3p increased PTEN expression and reduced p-JNK and p-c-Jun levels, thereby inhibiting MC proliferation and ameliorating renal lesions in IgAN. Moreover, these changes could be attenuated by co-transfection with PTEN siRNA. Collectively, these results illustrated that miR-214-3p accelerated MC proliferation in IgAN by directly targeting PTEN to modulate JNK/c-Jun signaling. Therefore, miR-214-3p may represent a novel therapeutic target for IgAN. Ivyspring International Publisher 2021-07-31 /pmc/articles/PMC8416718/ /pubmed/34512151 http://dx.doi.org/10.7150/ijbs.61274 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Li, Yan
Xia, Ming
Peng, Liang
Liu, Haiyang
Chen, Guochun
Wang, Chang
Yuan, Du
Liu, Yu
Liu, Hong
Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy
title Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy
title_full Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy
title_fullStr Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy
title_full_unstemmed Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy
title_short Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy
title_sort downregulation of mir‑214-3p attenuates mesangial hypercellularity by targeting pten‑mediated jnk/c-jun signaling in iga nephropathy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416718/
https://www.ncbi.nlm.nih.gov/pubmed/34512151
http://dx.doi.org/10.7150/ijbs.61274
work_keys_str_mv AT liyan downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy
AT xiaming downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy
AT pengliang downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy
AT liuhaiyang downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy
AT chenguochun downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy
AT wangchang downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy
AT yuandu downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy
AT liuyu downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy
AT liuhong downregulationofmir2143pattenuatesmesangialhypercellularitybytargetingptenmediatedjnkcjunsignalinginiganephropathy