miR‑181a‑5p regulates the proliferation and apoptosis of glomerular mesangial cells by targeting KLF6
Affiliations: Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200127, P.R. China
- Published online on: May 21, 2020 https://doi.org/10.3892/etm.2020.8780
Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
Diabetic nephropathy (DN) is a chronic loss of kidney function that frequently occurs in patients with diabetes mellitus and is characterized by abnormal glomerular mesangial cell (GMC) proliferation and apoptosis. By using microarray analysis, microRNA (miR)‑181a‑5p has previously been identified to be dysregulated in DN. The present study aimed to determine the underlying molecular mechanisms and function of miR‑181a‑5p in GMCs under DN conditions. First, reverse transcription‑quantitative PCR was performed to detect miR‑181a‑5p and kruppel‑like factor 6 (KLF6) expression in GMCs following high‑glucose treatment. Subsequently, MTT and flow cytometric assays were performed in order to determine the effect of miR‑181a‑5p and KLF6 on high‑glucose‑driven GMC proliferation and apoptosis. After confirming that KLF6 was a target gene of miR‑181a‑5p via a bioinformatics analysis and luciferase reporter assay, the mRNA and protein expression levels of associated factors in different treatment groups were measured. The results demonstrated that miR‑181a‑5p was significantly downregulated, while KLF6 was significantly upregulated in GMCs following treatment with high glucose. Furthermore, overexpression of miR‑181a led to suppression of cell proliferation and promoted apoptosis of GMCs induced by high glucose, while these effects were inhibited by co‑transfection with KLF6. Finally, miR‑181‑5p was demonstrated to inhibit the expression of KLF6, Bcl‑2, Wnt1 and β‑catenin, while increasing the expression levels of Bax and caspase‑3. In conclusion, the expression levels of miR‑181a‑5p were downregulated in GMCs following treatment with high glucose and overexpression of miR‑181a‑5p may inhibit GMC proliferation and promote apoptosis, at least partially through targeting KLF6 via the Wnt/β‑catenin signaling pathway. Overall, the results of the present study suggest that miR‑181a‑5p may have a crucial role in the occurrence and development of DN and may be a valuable diagnostic marker and therapeutic target for DN.