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  2. Expressions and related mechanisms of miR-212 and KLF4 in rats with acute kidney injury

Expressions and related mechanisms of miR-212 and KLF4 in rats with acute kidney injury

  • Mol Cell Biochem. 2021 Apr;476(4):1741-1749. doi: 10.1007/s11010-020-04016-x.
Xingguan Yang 1 Bo Li 2 Yu Guan 3 Hua-Mao Jiang 4
Affiliations

Affiliations

  • 1 Department of Urology Surgery, Jinan University, Guangzhou, 510632, People's Republic of China.
  • 2 Department of Drug Administration Section, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121099, People's Republic of China.
  • 3 Department of Critical Care Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121099, People's Republic of China.
  • 4 Department of Urology Surgery, The Second Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, People's Republic of China. huamaojiang12345@gmail.com.
Abstract

Acute kidney injury (AKI) occurs in 30%-70% of critically ill patients. Multiple organ failure (MOF), which is most often secondary to hypotension and septicemia, is a global public health problem. The prognosis of patients is poor. Currently, there is no specific therapeutic method. Finding new therapeutic targets is significant to improve the prognosis of AKI patients. This study explores expressions and related mechanisms of miR-212 and Kruppel-like factor 4 (KLF4) in rats with AKI. Sixty Wistar rats were randomly divided into 6 groups: Control group, sham operation group, model group, miR-212-agomir group, miR-212-antagomir group, miR-212-agomir+APTO-253 (joint group), n = 10. The expressions of miR-212, KLF4, inflammatory factors [tumor necrosis factor α (TNF-α), interleukin 6 (IL-6)], oxidative stress factors [superoxide dismutase (SOD), malondialdehyde (MDA)], and apoptosis-related proteins (Bax, Bcl-2) in renal tissue of rats were detected, and the relationship between miR-212 and KLF4 and the severity of AKI in rats were analyzed. The expression level of miR-212 increased (P < 0.05) and the expression level of KLF4 decreased (P < 0.05) in renal tissue of rats with AKI. miR-212 was negatively correlated with KLF4 expression (P < 0.05). MiR-212 was positively correlated with expressions of TNF-α, IL-6, MDA, and Bax (P < 0.05), negatively correlated with expressions of SOD and Bcl-2 (P < 0.05), KLF4 was negatively correlated with expressions of TNF-α, IL-6, MDA and Bax (P < 0.05), and positively correlated with expressions of SOD and Bcl-2 (P < 0.05). MiR-212 mimics can inhibit the luciferase activity of Wt-KLF4 (P < 0.05), and miR-212 inhibitor can promote the luciferase activity of Wt-KLF4 (P < 0.05). Down-regulation of miR-212 plays a protective role by targeting up-regulation of KLF4 to inhibit renal tissue inflammation, oxidative stress, and Apoptosis in rats with AKI, which may be a potential target for clinical treatment of AKI in the future.

Keywords

Acute kidney injury; KLF4; Mechanism; Rats; miR-212.

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