miR‐34b‐3p protects against acute kidney injury in sepsis mice via targeting ubiquitin‐like protein 4A

Autor: Shu‐Yin He, Gang Wang, Ying‐Hao Pei, Hai‐Ping Zhu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Kaohsiung Journal of Medical Sciences, Vol 36, Iss 10, Pp 817-824 (2020)
Druh dokumentu: article
ISSN: 2410-8650
1607-551X
DOI: 10.1002/kjm2.12255
Popis: Abstract MicroRNAs (miRNAs) have been reported as a diagnostic markers for sepsis, and miRNAs have also been found to play a regulatory role in sepsis‐induced acute kidney injury (AKI). However, the regulatory effect and mechanism of miR‐34b‐3p on AKI remains elusive. First, sepsis mice with AKI was established via cecal ligation puncture (CLP), and verified through hematoxylin‐eosin staining, determination of tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6/1β and serum levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). Data showed that CLP‐induced mice demonstrated increased ALT, BUN, TNF‐α, IL‐1β, and IL‐6 with injured pathological morphology of kidney tissues. Second, lipopolysaccharide (LPS) treatment elevated TNF‐α, IL‐1β, and IL‐6 contents in rat mesangial cells (RMCs). MiR‐34b‐3p was downregulated in both CLP‐induced mice and LPS‐induced RMCs. Third, target gene of miR‐34b‐3p was verified as ubiquitin‐like protein 4A (UBL4A), and UBL4A was upregulated in LPS‐induced RMCs. MiR‐34b‐3p could inhibit UBL4A expression and decreased TNF‐α, IL‐1β and IL‐6 contents in LPS‐induced RMCs, while overexpression of UBL4A counteract with the suppressive effects of miR‐34b‐3p on the protein expression. Moreover, transcriptional activity of UBL4A‐induced NF‐κB was decreased by miR‐34b‐3p. Lastly, in vivo injection of miR‐34b‐3p agomir improved CLP‐induced kidney tissues injury with declined ALT, BUN, TNF‐α, IL‐1β, IL‐6, and UBL4A. In general, miR‐34b‐3p overexpression could alleviate AKI in sepsis mice through downregulation of UBL4A/NF‐κB, providing potential therapeutic strategy for AKI.
Databáze: Directory of Open Access Journals
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