Identifying key antioxidative stress factors regulating Nrf2 in the genioglossus with human umbilical cord mesenchymal stem-cell therapy

利用人脐带间充质干细胞疗法识别调节颏舌肌 Nrf2 的关键抗氧化应激因素

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作者:Haixian Guo, Yue Liu, Xinlu Yu, Na Tian, Yan Liu, Dan Yu

Abstract

Intermittent hypoxia in patients with obstructive sleep apnea (OSA) hypopnea syndrome (OSAHS) is associated with pharyngeal cavity collapse during sleep. The effect of human umbilical cord mesenchymal stem cells (HUCMSCs) on OSA-induced oxidative damage in the genioglossus and whether nuclear factor erythroid 2-related factor 2 (Nrf2) or its upstream genes play a key role in this process remains unclear. This study aimed to identify the key factors responsible for oxidative damage during OSAHS through Nrf2 analysis and hypothesize the mechanism of HUCMSC therapy. We simulated OSA using an intermittent hypoxia model, observed the oxidative damage in the genioglossus and changes in Nrf2 expression during intermittent hypoxia, and administered HUCMSCs therapy. Nrf2 initially increased, then decreased, aggravating the oxidative damage in the genioglossus; Nrf2 protein content decreased during hypoxia. Using transcriptomics, we identified seven possible factors in HUCMSCs involved in ameliorating oxidative stress by Nrf2, of which DJ-1 and MEF2A, showing trends similar to Nrf2, were selected by polymerase chain reaction. HUCMSCs may reduce oxidative stress induced by intermittent hypoxia through Nrf2, and the possible upstream target genes in this process are MEF2A and DJ-1. Further studies are needed to verify these findings.

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