MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-β1/Smad3 Signaling Pathway

Abstract

Background/Aims: We examined the effects of microRNA-27a (miR-27a) on detrusor fibrosis in streptozotocin (STZ)-induced diabetic rats. Methods: Eighty healthy Sprague-Dawley (SD) rats were randomly allocated into control, diabetic, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siRNA-PRKAA2 (siPRKAA2) and inhibitors + siPRKAA2 groups (the latter 7 groups were established as STZ-induced diabetic rat models and treated in different manners). Detrusor cell apoptosis in bladder tissues was determined through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. Detrusor cells were assigned to the blank, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siPRKAA2 and inhibitors + siPRKAA2 groups. Flow cytometry determined the cell cycle stage and apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting (WB) were used to assess the expression of miR-27a, PRKAA2, TGF-β1, Smad3, p-Smad3, fibronectin (FN), connective tissue growth (CTGF), and collagen-I (COL-I) in tissues and cells. Results: Compared with the control group, the diabetic, miR-27a mimics, and siPRKAA2 groups showed reduced weight and PRKAA2 expression, but elevated blood glucose, serum creatinine (sCr), blood urea nitrogen (BUN), cell apoptosis, and expression of TGF-β1, Smad3, FN, COL-I, CTGF, and p-Smad3. The opposite trend was observed in the miR-27a inhibitors group. PRKAA2 is a target gene of miR-27a. Compared to the blank group, the miR-27a mimics and siPRKAA2 groups indicated markedly increased TGF-β1, Smad3, FN, COL-I, CTGF and p-Smad3 expression; decreased PRKAA2 expression; and increased cell apoptosis. The miR-27a inhibitors group showed the opposite trend. Conclusion: These results indicate that miR-27a may contribute to detrusor fibrosis in STZ-induced diabetic rats by targeting PRKAA2 via the TGF-β1/Smad3 signaling pathway.

MicroRNA-744 Inhibits Proliferation of Bronchial Epithelial Cells by Regulating Smad3 Pathway via Targeting Transforming Growth Factor-β1 (TGF-β1) in Severe Asthma

“…In the present study, we found enhanced TGF-β1 facilitated bronchial epithelial cells proliferation in severe asthma. Emerging evidence suggests that miRNAs play a pivotal role in endothelial cells and detrusor fibrosis through the TGF-β1/Smad signaling pathway [38,39]. However, there is no direct evidence in support of the interaction between miR-744 and TGF-β1/Smad pathway.…”

Cardiac fibroblast miR‐27a may function as an endogenous anti‐fibrotic by negatively regulating Early Growth Response Protein 3 (EGR3)

“…One notable miRNA-miR-27a-is dysregulated in both animal models of fibrosis and human fibrotic disease. [16][17][18][19] Interestingly, miR-27a has been shown to suppress fibrosis in kidney, bladder, liver and lung pathologies. [16][17][18][19] These findings suggest that targeting miR-27a could constitute a possible method to prevent cardiac fibrosis.…”

MicroRNA-219c-5p regulates bladder fibrosis by targeting FN1

“…Numerous studies have shown that miRNAs are involved in the tissue fibrosis process. Jing Wu et al [33] reported that miR-27a can target the AMP-activated protein kinase alpha2 catalytic subunit and activate the TGF-β1 and Smad3 signaling pathways, thereby reducing detrusor fibrosis in streptozotocin-induced diabetic rats. Su-Jin Moon et al [34] reported that FN1 is an important functional protein in the development of skin fibers.…”