HIF‐1<i>α</i>‐Mediated miR‐623 Regulates Apoptosis and Inflammatory Responses of Nucleus Pulposus Induced by Oxidative Stress via Targeting TXNIP
Xiaogang Bao, Zhenhua Wang, Qi Jia, Sibo Shen, Likang Wu, Qi Jiang, Changwei Li, Guohua Xu
Abstract
Excessive apoptosis and inflammatory responses of nucleus pulposus (NP) cells induced by oxidative stress contribute to intervertebral disc degeneration (IVDD). Though some microRNAs are associated with IVDD, the specific microRNA that can mediate apoptotic and inflammatory responses of NP cells induced by oxidative stress synchronously still needs further identification. Here, we find that microRNA‐623 (miR‐623) is downregulated in IVDD and its expression is regulated by hypoxia‐inducible factor‐1 α (HIF‐1 α ) under oxidative stress conditions. Mechanistically, HIF‐1 α is observed to promote miR‐623 expression by directly binding to its promoter region (−1,994/−1,987 bp). Functionally, miR‐623 is found to work as an intermediator in alleviating apoptosis and inflammatory responses of NP cells induced by oxidative stress via regulating thioredoxin‐interacting protein ( TXNIP ) expression by directly targeting its 3 ′ ‐untranslated region (3 ′ ‐UTR). Thus, on elucidating the expression and functional mechanisms of miR‐623, our study suggests that miR‐623 can be a valuable therapeutic target for treating oxidative stress‐induced IVDD.