Role of promoting inflammation of Krüppel-like factor 6 in acute kidney injury

Ren Fail. 2020 Nov;42(1):693-703. doi: 10.1080/0886022X.2020.1793353.

Abstract

Background: Krüppel-like factor 6 (KLF6) is a transcription factor that participate in various pathophysiological processes, but its contribution in ischemia acute kidney injury (AKI) is lacking so far. The study aimed to investigate the expression and the role of KLF6 in kidney ischemia-reperfusion (IR) injury.

Method: Microarray data were collected from GSE58438 and GSE52004. The rat IR model was established to evaluate the mRNA and protein expression of KLF6 and inflammatory cytokines in serum and kidney tissues. SiRNA-KLF6 was transfected with HK-2 cells, and then a cell-based hypoxia-reoxygenation (HR) model was established.

Results: Bioinformatics showed KLF6 mRNA in kidney tissue is up-regulated in 3 h after IR in rat kidney, which involved in cell activation, leukocyte activation, and response to hydrogen peroxide after IR. The rat IR model results showed that KLF6 expression was peaking at 6 h, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α was increased both in serum and kidney tissues, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed that KLF6 knock-down reduced the pro-inflammatory cytokines expression.

Conclusion: These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) KLF6 may play a role in promoting inflammation in AKI.

Keywords: Krüppel-like factor 6; acute kidney injury; inflammation; ischemia–reperfusion injury; proximal tubule epithelial cells.

MeSH terms

  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Cell Line
  • Cytokines / metabolism
  • Inflammation / metabolism*
  • Kruppel-Like Factor 6 / genetics
  • Kruppel-Like Factor 6 / metabolism*
  • Male
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Transcription Factors / metabolism
  • Up-Regulation

Substances

  • Biomarkers
  • Cytokines
  • Klf6 protein, rat
  • Kruppel-Like Factor 6
  • RNA, Small Interfering
  • Transcription Factors

Grants and funding

This study was supported by the National Natural Science Foundation of China (81770679), China.