Downregulation of microRNA-23b protects against ischemia-reperfusion injury via p53 signaling pathway by upregulating MDM4 in rats.
Total knee arthroplasty is a commonly performed safe procedure and typically executed in severe knee arthritis, but it also triggers ischemia-reperfusion injury (IRI). More recently, microRNAs (miRs) have been reported to play a contributory role in IRI through the key signaling pathway. Hence, the current study aimed to investigate the effect and specific mechanism of microRNA-23b (miR-23b), murine double minute 4 (MDM4), and the p53 signaling pathway in IRI rat models. First, the IRI model was established, and the expression pattern of miR-23b, MDM4, and the p53 signaling pathway-related genes was characterized in cartilaginous tissues. Then, miR-23b mimics or inhibitors were applied for the elevation or the depletion of the miR-23b expression and siRNA-MDM4 for the depletion of the MDM4 expression in the articular chondrocytes. By means of immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot analysis, IRI rats exhibited increased miR-23b expression, activated p53 signaling pathway, and decreased MDM4 expression. MDM4 was verified as a target gene of miR-23b through. Downregulated miR-23b increased the expression of MDM4, AKT, and Bcl-2, but decreased the expression of p53, p21, and Bax. In addition, a series of cell experiments demonstrated that downregulated miR-23b promoted articular chondrocyte proliferation and cell cycle entry, but inhibited articular chondrocyte apoptosis. The absence of the effects of miR-23b was observed after MDM4 knocked down. Our results indicate that silencing miR-23b could act to attenuate IRI and reduce the apoptosis of articular chondrocytes through inactivation of the p53 signaling pathway by upregulating MDM4, which provide basic therapeutic considerations for a novel target against IRI.
['Zhao|Zhi|Z|', 'Guan|Jian-Zhong|JZ|', 'Wu|Min|M|0000-0001-7741-7021', 'Lai|Gui-Hua|GH|', 'Zhu|Zhong-Lian|ZL|']
D000818:Animals D002356:Cartilage D002357:Cartilage Diseases D018797:Cell Cycle Proteins D049109:Cell Proliferation D019902:Chondrocytes D015536:Down-Regulation D035683:MicroRNAs D051381:Rats D017207:Rats, Sprague-Dawley D015427:Reperfusion Injury D015398:Signal Transduction D016159:Tumor Suppressor Protein p53
p53 signaling pathway ischemia-reperfusion injury (IRI) microRNA-23b (miR-23b) murine double minute 4 (MDM4) articular chondrocytes