Department of Cardiothoracic Surgery, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Putuo District, Shanghai, 200092, China.
Department of Medical Institution Conducting Clinical Trials for Human Used Drug, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, 046099, Shanxi, China.
Funct Integr Genomics. 2022 Dec;22(6):1297-1306. doi: 10.1007/s10142-022-00879-z. Epub 2022 Aug 1.
Pulmonary fibrosis (PF) is a chronic lung disorder, in which the mechanism of mmu-microRNA (miR)-92a-3p is not elucidated clearly. The present work was proposed to disclose mmu-miR-92a-3p-focused mechanism in PF with cytoplasmic polyadenylation element-binding protein 4 (Cpeb4)/Smad2/3 axis. PF was induced in mice by the intratracheal injection of bleomycin (BLM). Then, the BLM-treated mice were injected with mmu-miR-92a-3p- and/or Cpeb4-related adenovirus vectors. mmu-miR-92a-3p, Cpeb4, and Smad2/3 expression in lung tissues were examined. Alveolar cell apoptosis and collagen deposition in lung tissues and inflammatory factors in serum were observed. The interaction between mmu-miR-92a-3p and Cpeb4 was explored. Lowly expressed mmu-miR-92a-3p and highly expressed Cpeb4 and Smad2/3 were manifested in BLM-induced PF mice. BLM-induced PF mice exhibited enhanced inflammation, alveolar cell apoptosis, and collagen deposition, which would be attenuated by upregulating mmu-miR-92a-3p or downregulating Cpeb4. mmu-miR-92a-3p targeted Cpeb4. Upregulating mmu-miR-92a-3p or downregulating Cpeb4 inactivated the Smad2/3 signaling pathway in BLM-induced PF mice. It is elaborated that mmu-miR-92a-3p attenuates the process of PF by modulating Cpeb4-mediated Smad2/3 signaling pathway, renewing the molecular mechanism of PF.
肺纤维化（PF）是一种慢性肺部疾病，其 mmu-微小 RNA（miR）-92a-3p 的机制尚不清楚。本研究旨在通过细胞质多聚腺苷酸化元件结合蛋白 4（Cpeb4）/Smad2/3 轴揭示 PF 中 mmu-miR-92a-3p 的作用机制。通过气管内注射博来霉素（BLM）诱导小鼠 PF。然后，用 mmu-miR-92a-3p 和/或 Cpeb4 相关腺病毒载体对 BLM 处理的小鼠进行注射。检测肺组织中 mmu-miR-92a-3p、Cpeb4 和 Smad2/3 的表达。观察肺组织中肺泡细胞凋亡和胶原沉积以及血清中炎症因子的变化。探索 mmu-miR-92a-3p 与 Cpeb4 之间的相互作用。BLM 诱导的 PF 小鼠中 mmu-miR-92a-3p 表达下调，Cpeb4 和 Smad2/3 表达上调。BLM 诱导的 PF 小鼠表现出炎症增强、肺泡细胞凋亡和胶原沉积，上调 mmu-miR-92a-3p 或下调 Cpeb4 可减轻这些变化。mmu-miR-92a-3p 靶向 Cpeb4。上调 mmu-miR-92a-3p 或下调 Cpeb4 可使 BLM 诱导的 PF 小鼠中 Smad2/3 信号通路失活。综上所述，mmu-miR-92a-3p 通过调节 Cpeb4 介导的 Smad2/3 信号通路减轻 PF 进程，为 PF 的分子机制提供了新的认识。
