miR-130b-3p involved in the pathogenesis of age-related hearing loss via targeting PPARγ and autophagy
作者全名：Zhang, Juhong; Sun, Wenfang; Kuang, Shaojing; Gan, Qiang; Li, Hai; Ma, Haizhu; Yang, Guijun; Guo, Jialin; Tang, Yong; Yuan, Wei
作者地址：[Zhang, Juhong; Sun, Wenfang; Kuang, Shaojing; Ma, Haizhu; Yang, Guijun; Guo, Jialin; Yuan, Wei] Chongqing Univ, Chongqing Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Chongqing 401147, Peoples R China; [Gan, Qiang] Chongqing Nanchuan Dist Tradit Chinese Med Hosp, Dept Otorhinolaryngol, Chongqing 408499, Peoples R China; [Li, Hai] Xuanhan Cty Peoples Hosp, Dept Otorhinolaryngol Head & Neck Surg, Dazhou 636150, Xuanhan County, Peoples R China; [Tang, Yong] Chongqing Med Univ, Sch Basic Med, Dept Histol & Embryol, Chongqing 400016, Peoples R China; [Yuan, Wei] Chongqing Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, 118 Xingguang Ave, Chongqing 401147, Peoples R China
通信作者：Yuan, W (通讯作者)，Chongqing Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, 118 Xingguang Ave, Chongqing 401147, Peoples R China.
来源：HEARING RESEARCH
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001248474500001
JCR分区：Q1
影响因子：2.5
年份：2024
卷号：449
期号：
开始页：
结束页：
文献类型：Article
关键词：Age-related hearing loss; MiR-130b-3p; PPAR gamma; Autophagy
摘要：The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting PPAR gamma. We constructed miR-130b-3p knockout (antagomir) and PPAR gamma over-expression (OE-PPAR gamma) mice model by injecting mmu-miR-130b-3p antagomir and HBAAV2/Anc80-m-Pparg-T2A-mCHerry into the right ear' round window of each mouse, respectively. In vitro, we introduced oxidative stress within HEI-OC1 cells by H2O2 and exogenously changed the miR-130b-3p and PPAR gamma levels. MiRNA level was detected by RT-qPCR, proteins by western blotting and immunohistochemistry. Morphology of autophagosomes was observed by electron microscopy. In vivo, the cochlea of aged mice showed higher miR-130b-3p expression and lower PPAR gamma expression, while exogenous inhibition of miR-130b-3p up-regulated PPAR gamma expression. Autophagy-related biomarkers expression (ATG5, Beclin-1 and LC3B II/I) decreased in aged mice, which reversely increased after the inhibition of miR-130b3p. The elevation of PPAR gamma demonstrated similar effects. Contrarily, exogenous overexpression of miR-130b3p resulted in the decrease of ATG5, Beclin-1 and LC3B II/I. We created oxidative stress within HEI-OC1 by H2O2, subsequently observed the formation of autophagosomes under electron microscope, so as the elevated cell apoptosis rate and weakened cell viability. MiR-130b-3p/PPAR gamma contributed to the premature senescence of these H2O2-induced HEI-OC1 cells. MiR-130b-3p regulated HEI-OC1 cell growth by targeting PPAR gamma, thus leading to ARHL.
基金机构：The 69th batch of China Postdoctoral Science Foundation; Second class of the "regional special support plan" [2021M693922]; Middle-aged medical high-end talents in Chongqing (The 7th batch) , Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) [2022MSXM046, 2022DBXM006]; Chongqing Technology Innovation and Application Development Special Project [CSTB2023TIAD-KPX0059]; Chongqing young and middle-aged medical excellence team [2000109-02]; Chongqing Talents-Innovative leading talents in the medical field [cstc2022ycjh-bgzxm0126]
基金资助正文：This study was supported by the 69th batch of China Postdoctoral Science Foundation, the second class of the "regional special support plan" (No. 2021M693922) , 2021 Young and middle-aged medical high-end talents in Chongqing (The 7th batch) , Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) (No. 2022MSXM046, No. 2022DBXM006) , Chongqing Technology Innovation and Application Development Special Project (No. CSTB2023TIAD-KPX0059) , Chongqing young and middle-aged medical excellence team (The 1st batch, 2000109-02) , and Chongqing Talents-Innovative leading talents in the medical field (No. cstc2022ycjh-bgzxm0126) .
