MiR‑519d‑3p promotes TGFβ/Smad mediated postoperative epidural scar formation via suppression of BAMBI.

Abstract

To investigate the role of microRNA (miR)‑519d‑3p in postoperative epidural scar formation and its regulation of the bone morphogenetic protein and activin membrane‑bound inhibitor (BAMBI), miR‑519d‑3p and BAMBI expression levels in the lumbar disc of patients who had undergone laminectomy were detected with reverse transcription‑quantitative polymerase chain reaction and western blotting. The results demonstrated that miR‑519d‑3p expression was significantly increased, whereas BAMBI expression was sharply reduced in the lumbar discs of patients suffering from epidural scars. Subsequently, the miR‑519d‑3p mimic was transfected into primary fibroblasts isolated from epidural scar tissues. Flow cytometric and Cell Countin Kit‑8 analyses indicated that overexpression of miR‑519d‑3p promoted the proliferation of fibroblasts, the production of tumor necrosis factor‑α and interleukin (IL)‑1α, and the expression of typeI collagen(colI), α‑smooth muscle actin (α‑SMA) and fibronectin(FN). Downregulation of miR‑519d‑3p by the miR‑519d‑3p antagomir transfection had the opposite effect. Bioinformatics and luciferase reporter gene analyses demonstrated that BAMBI is a target gene of miR‑519d‑3p: miR‑519d‑3p directly binds to the 3'‑untranslated region of BAMBI mRNA and suppressed BAMBI protein expression. Finally, the pcDNA‑BAMBI vector and BAMBI small interfering RNA were respectively transfected into primary fibroblasts to overexpress and knockdown the BAMBI gene. It was demonstrated that BAMBI overexpression suppressed fibroblast proliferation, TNF‑α and IL‑1α production, and the expression of colI, α‑SMA and FN proteins, whereas, BAMBI knockdown had the opposite effect. In conclusion, it was noted that BAMBI is a target of miR‑519d‑3p and miR‑519d‑3p promotes transforming growth factor β/mothers against decapentaplegic homolog9‑mediated postoperative epidural scar formation via suppression of BAMBI.