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miR−122−5p Regulates Renal Fibrosis In Vivo

The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcrip...

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Autores principales: Kaneko, Shohei, Yanai, Katsunori, Ishii, Hiroki, Aomatsu, Akinori, Hirai, Keiji, Ookawara, Susumu, Ishibashi, Kenichi, Morishita, Yoshiyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736395/
https://www.ncbi.nlm.nih.gov/pubmed/36499744
http://dx.doi.org/10.3390/ijms232315423
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author Kaneko, Shohei
Yanai, Katsunori
Ishii, Hiroki
Aomatsu, Akinori
Hirai, Keiji
Ookawara, Susumu
Ishibashi, Kenichi
Morishita, Yoshiyuki
author_facet Kaneko, Shohei
Yanai, Katsunori
Ishii, Hiroki
Aomatsu, Akinori
Hirai, Keiji
Ookawara, Susumu
Ishibashi, Kenichi
Morishita, Yoshiyuki
author_sort Kaneko, Shohei
collection PubMed
description The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction showed that miR−122−5p was the most downregulated (0.28-fold) miRNA in the kidneys of UUO mice. The injection of an miR−122−5p mimic promoted renal fibrosis and upregulated COL1A2 and FN1, whereas an miR−122−5p inhibitor suppressed renal fibrosis and downregulated COL1A2 and FN1. The expression levels of fibrosis-related mRNAs, which were predicted targets of miR−122−5p, were evaluated. The expression level of TGFBR2, a pro-fibrotic mRNA, was upregulated by the miR−122−5p mimic, and the expression level of FOXO3, an anti−fibrotic mRNA, was upregulated by the miR−122−5p inhibitor. The protein expressions of TGFBR2 and FOXO3 were confirmed by immunohistochemistry. Additionally, the expression levels of LC3, downstream anti-fibrotic mRNAs of FOXO3, were upregulated by the miR−122−5p inhibitor. These results suggest that miR−122−5p has critical roles in renal fibrosis.
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spelling pubmed-97363952022-12-11 miR−122−5p Regulates Renal Fibrosis In Vivo Kaneko, Shohei Yanai, Katsunori Ishii, Hiroki Aomatsu, Akinori Hirai, Keiji Ookawara, Susumu Ishibashi, Kenichi Morishita, Yoshiyuki Int J Mol Sci Article The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction showed that miR−122−5p was the most downregulated (0.28-fold) miRNA in the kidneys of UUO mice. The injection of an miR−122−5p mimic promoted renal fibrosis and upregulated COL1A2 and FN1, whereas an miR−122−5p inhibitor suppressed renal fibrosis and downregulated COL1A2 and FN1. The expression levels of fibrosis-related mRNAs, which were predicted targets of miR−122−5p, were evaluated. The expression level of TGFBR2, a pro-fibrotic mRNA, was upregulated by the miR−122−5p mimic, and the expression level of FOXO3, an anti−fibrotic mRNA, was upregulated by the miR−122−5p inhibitor. The protein expressions of TGFBR2 and FOXO3 were confirmed by immunohistochemistry. Additionally, the expression levels of LC3, downstream anti-fibrotic mRNAs of FOXO3, were upregulated by the miR−122−5p inhibitor. These results suggest that miR−122−5p has critical roles in renal fibrosis. MDPI 2022-12-06 /pmc/articles/PMC9736395/ /pubmed/36499744 http://dx.doi.org/10.3390/ijms232315423 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kaneko, Shohei
Yanai, Katsunori
Ishii, Hiroki
Aomatsu, Akinori
Hirai, Keiji
Ookawara, Susumu
Ishibashi, Kenichi
Morishita, Yoshiyuki
miR−122−5p Regulates Renal Fibrosis In Vivo
title miR−122−5p Regulates Renal Fibrosis In Vivo
title_full miR−122−5p Regulates Renal Fibrosis In Vivo
title_fullStr miR−122−5p Regulates Renal Fibrosis In Vivo
title_full_unstemmed miR−122−5p Regulates Renal Fibrosis In Vivo
title_short miR−122−5p Regulates Renal Fibrosis In Vivo
title_sort mir−122−5p regulates renal fibrosis in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736395/
https://www.ncbi.nlm.nih.gov/pubmed/36499744
http://dx.doi.org/10.3390/ijms232315423
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