Objective: To explore the effects of LncRNA TUG1 on renal fibrosis in diabetic nephropathy(DN) rats and its potential molecular mechanism. Methods: The DN rat model was constructed by streptozotocin. LncRNA expression profiling was used to explore differentially expressed LncRNA in kidney tissues of DN rats. Lentivirus assay was applied to overexpress LncRNA TUG1 in DN rats. Hematoxylin-eosin(HE) staining was used to detect the histomorphological changes of overexpressed LncRNA TUG1 on DN rat kidney tissues. The effect of LncRNA TUG1 overexpression on mRNA expression levels of miR-21, fibronectin(FN), collagen type Ⅳ(Col-4) and transforming growth factor β1(TGFβ1) were detected by real time quantitative polymerase chain reaction(RT-qPCR). The protein expression levels of FN, Col-4, TGFβ1, phosphatase and tensin homolog(PTEN), phosphatidylin-ositol-3-kinase(p-PI3K) and Phosphorylated-Akt(p-Akt) proteins was assayed by Western blot assay. Bioinformatics software was applied to predict the interaction of miR-21 and LncRNA TUG1, and luciferin reporter assay method was used to verify the interaction between miR-21 and LncRNA TUG1. A high glucose-induced glomerular thylakoid HBZY-1 cell model was constructed. In HBZY-1 cells, LncRNA TUG1 was overexpressed using a lentivirus assay, cells were treated with miR-21 mimic, and then CCK-8 assay was used to detect their effect on cell proliferation. Their effect on the expression levels of FN, Col-4, and TGFβ1 mRNA was subsequently detected using RT-qPCR. Results: The expression level of LncRNA TUG1 was significantly reduced in renal tissue of DN rats. Overexpression of LncRNA TUG1 inhibited the mRNA and protein expression levels of FN, Col-4 and TGFβ1 in DN rats, and the pathological morphology of renal tissue was significantly improved. The results of dual luciferase reporter assay showed that LncRNA TUG1 bound to miR-21 through a direct targeting manner. Overexpression of LncRNA TUG1 inhibited the expression of miR-21, further upregulated PTEN and may inhibit the phosphatidylinositol 3-kinase/protein kinase(PI3K/Akt) signaling pathway. In addition, overexpression of LncRNA TUG1 inhibited the proliferation of HBZY-1 cells and suppressed the expression levels of FN, Col-4, and TGFβ1 mRNA in HBZY-1 cells. However, treatment with miR-21 mimic can reverse the proliferation inhibition and fibrosis suppression effects of LncRNA TUG1 overexpression. Conclusion: LncRNA TUG1 regulates miR-21/PTEN axis to inhibit renal fibrosis in DN rats.
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