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30 October 2019 : Laboratory Research  

miR-34b Alleviates High Glucose-Induced Inflammation and Apoptosis in Human HK-2 Cells via IL-6R/JAK2/STAT3 Signaling Pathway

Na Lv1BCDE*, Chunqing Li1BCDF, Xin Liu1BEF, Caihui Qi1ABCDE, Zhenqing Wang1ACD

DOI: 10.12659/MSM.917128

Med Sci Monit 2019; 25:8142-8151

Abstract

BACKGROUND: It is well established that inflammation and apoptosis of renal tubular epithelial cells caused by hyperglycemia contribute to the development of diabetic nephropathy (DN). Although microRNAs (miRNAs) are known to have roles in inflammation-related disorders, the exact role of miR-34b in DN has not been defined, and the regulatory mechanism has been unclear. This study aimed to clarify the role of miR-34b in DN pathogenesis.

MATERIAL AND METHODS: Expression of miR-34b, IL-6R, and other key factors of inflammation, apoptosis (TNF-α, IL-1β, IL-6, caspase-3) in high glucose (HG)-induced HK-2 cells were measured by real-time PCR, Western blot, and flow cytometric cell apoptosis assays. We used luciferase reporter assay to detect the target of miR-34b. Moreover, the targeting gene of miR-34b and its downstream JAK2/STAT3 signaling pathway were explored.

RESULTS: It was demonstrated that miR-34b overexpression inhibited apoptosis and expression levels of TNF-α, IL-1β, IL-6, and caspase-3 in HG-treated HK-2 cells. We also found that IL-6R is a direct target of miR-34b, which could rescue inflammation and apoptosis in HG-treated HK-2 cells transfected with miR-34b mimic. Furthermore, we showed that overexpression of miR-34b inhibited the IL-6R/JAK2/STAT3 signaling pathway in HG-treated HK-2 cells.

CONCLUSIONS: Our data suggest that overexpression of miR-34b improves inflammation and ameliorates apoptosis in HG-induced HK-2 cells via the IL-6R/JAK2/STAT3 pathway, indicating that miR-34b could be a promising therapeutic target in DN.

Keywords: Apoptosis, MicroRNAs, Down-Regulation, Glucose, Hyperglycemia, Janus Kinase 2, Receptors, Interleukin-6, STAT3 Transcription Factor, Signal Transduction

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750