Cargando…
miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury
OBJECTIVE: This study was designed to uncover the mechanism of miR-34b-5p-mediated aquaporin-2 (AQP2) in sepsis-induced injury using human renal tubular epithelial cells (HK-2). METHODS: Serum levels of miR-34b-5p, TNF-α, IL-1β, IL-6, serum creatinine (SCr), and blood urea nitrogen (BUN) in septic p...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850462/ https://www.ncbi.nlm.nih.gov/pubmed/33494641 http://dx.doi.org/10.1080/0886022X.2021.1871922 |
_version_ | 1783645448998748160 |
---|---|
author | Zheng, Caifa Wu, Dansen Shi, Songjing Wang, Liming |
author_facet | Zheng, Caifa Wu, Dansen Shi, Songjing Wang, Liming |
author_sort | Zheng, Caifa |
collection | PubMed |
description | OBJECTIVE: This study was designed to uncover the mechanism of miR-34b-5p-mediated aquaporin-2 (AQP2) in sepsis-induced injury using human renal tubular epithelial cells (HK-2). METHODS: Serum levels of miR-34b-5p, TNF-α, IL-1β, IL-6, serum creatinine (SCr), and blood urea nitrogen (BUN) in septic patients with acute kidney injury (AKI) and healthy controls were detected. Lipopolysaccharide (LPS) was used to induce sepsis in HK-2 cells. LPS-induced HK-2 cells were transfected with miR-34b-5p inhibitor, miR-34b-5p mimic, pcDNA3.1-AQP2, si-AQP2, miR-34b-5p inhibitor + si-NC, or miR-34b-5p inhibitor + si-AQP2. The expressions of miR-34b-5p, AQP2, Bax, Bcl-2, cleaved caspase-3, TNF-α, IL-1β, and IL-6 in HK-2 cells were detected. TUNEL staining revealed the apoptosis of HK-2 cells. Dual-luciferase reporter assay verified the binding between miR-34b-5p and AQP2. RESULTS: The expression of miR-34b-5p and the inflammatory responses were augmented in septic AKI patients. miR-34b-5p was up-regulated and AQP2 was down-regulated in LPS-induced HK-2 cells. miR-34b-5p inhibition or AQP2 overexpression ameliorated apoptosis and inflammation in LPS-induced HK-2 cells. In contrast, overexpressing miR-34b-5p deteriorated LPS-induced injury in HK-2 cells. AQP2 was a downstream target of miR-34b-5p. AQP2 silencing abolished the suppressive effects of miR-34b-5p inhibition on LPS-induced apoptosis and inflammatory response in HK-2 cells. CONCLUSION: miR-34b-5p inhibits AQP2 to promote LPS-induced injury in HK-2 cells. |
format | Online Article Text |
id | pubmed-7850462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-78504622021-02-05 miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury Zheng, Caifa Wu, Dansen Shi, Songjing Wang, Liming Ren Fail Laboratory Study OBJECTIVE: This study was designed to uncover the mechanism of miR-34b-5p-mediated aquaporin-2 (AQP2) in sepsis-induced injury using human renal tubular epithelial cells (HK-2). METHODS: Serum levels of miR-34b-5p, TNF-α, IL-1β, IL-6, serum creatinine (SCr), and blood urea nitrogen (BUN) in septic patients with acute kidney injury (AKI) and healthy controls were detected. Lipopolysaccharide (LPS) was used to induce sepsis in HK-2 cells. LPS-induced HK-2 cells were transfected with miR-34b-5p inhibitor, miR-34b-5p mimic, pcDNA3.1-AQP2, si-AQP2, miR-34b-5p inhibitor + si-NC, or miR-34b-5p inhibitor + si-AQP2. The expressions of miR-34b-5p, AQP2, Bax, Bcl-2, cleaved caspase-3, TNF-α, IL-1β, and IL-6 in HK-2 cells were detected. TUNEL staining revealed the apoptosis of HK-2 cells. Dual-luciferase reporter assay verified the binding between miR-34b-5p and AQP2. RESULTS: The expression of miR-34b-5p and the inflammatory responses were augmented in septic AKI patients. miR-34b-5p was up-regulated and AQP2 was down-regulated in LPS-induced HK-2 cells. miR-34b-5p inhibition or AQP2 overexpression ameliorated apoptosis and inflammation in LPS-induced HK-2 cells. In contrast, overexpressing miR-34b-5p deteriorated LPS-induced injury in HK-2 cells. AQP2 was a downstream target of miR-34b-5p. AQP2 silencing abolished the suppressive effects of miR-34b-5p inhibition on LPS-induced apoptosis and inflammatory response in HK-2 cells. CONCLUSION: miR-34b-5p inhibits AQP2 to promote LPS-induced injury in HK-2 cells. Taylor & Francis 2021-01-25 /pmc/articles/PMC7850462/ /pubmed/33494641 http://dx.doi.org/10.1080/0886022X.2021.1871922 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Laboratory Study Zheng, Caifa Wu, Dansen Shi, Songjing Wang, Liming miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury |
title | miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury |
title_full | miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury |
title_fullStr | miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury |
title_full_unstemmed | miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury |
title_short | miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury |
title_sort | mir-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury |
topic | Laboratory Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850462/ https://www.ncbi.nlm.nih.gov/pubmed/33494641 http://dx.doi.org/10.1080/0886022X.2021.1871922 |
work_keys_str_mv | AT zhengcaifa mir34b5ppromotesrenalcellinflammationandapoptosisbyinhibitingaquaporin2insepsisinducedacutekidneyinjury AT wudansen mir34b5ppromotesrenalcellinflammationandapoptosisbyinhibitingaquaporin2insepsisinducedacutekidneyinjury AT shisongjing mir34b5ppromotesrenalcellinflammationandapoptosisbyinhibitingaquaporin2insepsisinducedacutekidneyinjury AT wangliming mir34b5ppromotesrenalcellinflammationandapoptosisbyinhibitingaquaporin2insepsisinducedacutekidneyinjury |