2. Academic Validation
  3. MiR-1307-5p enhances fibroblast transdifferentiation to exacerbate chronic obstructive pulmonary disease through regulating FBXL16/HIF1α axis

MiR-1307-5p enhances fibroblast transdifferentiation to exacerbate chronic obstructive pulmonary disease through regulating FBXL16/HIF1α axis

  • Respir Res. 2024 Oct 17;25(1):376. doi: 10.1186/s12931-024-03007-6.
Li-Peng Yao # 1 2 3,  Zheng-Kai Wang # 1 3,  Xin-Qing Jiang # 4,  Beier Jiang # 5,  Si-Jia Chen 5,  Zhi-Dan Hua 3,  Dan-Dan Gao 1,  Quan Zheng 5,  Sheng-Mei Zhu 5,  Mao-Xiang Qian 6,  Feng Zhang 7,  Li-Feng Xu 8,  Cheng-Shui Chen 9 10 11,  Fang Lu 12
Affiliations

Affiliations

  • 1 Wenzhou Medical University, Wenzhou, 325035, China.
  • 2 Ningbo College of Health Sciences, Ningbo, 315000, China.
  • 3 Department of Respiratory and Critical Care, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China.
  • 4 Zhejiang Chinese Medical University, the 2nd Clinical Medical College, Hangzhou, 310053, China.
  • 5 Joint Innovation Center for Engineering in Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China.
  • 6 Institute of Pediatrics and Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai, 200032, China.
  • 7 Joint Innovation Center for Engineering in Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China. fengzhang@wmu.edu.cn.
  • 8 Joint Innovation Center for Engineering in Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China. qz1109@wmu.edu.cn.
  • 9 Wenzhou Medical University, Wenzhou, 325035, China. wzchencs@163.com.
  • 10 Department of Respiratory and Critical Care, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China. wzchencs@163.com.
  • 11 The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, Centre of Precision Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China. wzchencs@163.com.
  • 12 Department of Respiratory and Critical Care, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China. lufang@wmu.edu.cn.
  • # Contributed equally.
PMID: 39420370 DOI: 10.1186/s12931-024-03007-6
Abstract

Chronic obstructive pulmonary disease (COPD) is an irreversible and progressive chronic inflammatory lung disease which affects millions of people worldwide. Activated fibroblasts are observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition. In this study, we identified that miR-1307-5p expression was significantly increased in lung fibroblasts derived from COPD patients. Mechanistically, we found that upregulation of miR-1307-5p promoted TGF-β induced lung fibroblast activation and transdifferentiation. We also identified FBXL16 as a direct target for miR-1307-5p mediated myofibroblast activation in COPD. Knockdown of FBXL16 by siRNA prominently increased the expression of myofibroblast markers in MRC-5 fibroblasts after TGF-β administration. Ectopic expression of FBXL16 in MRC-5 counteracted miR-1307-5p agomir-induced fibroblast transdifferentiation. Furthermore, We found that miR-1307-5p promoted pulmonary fibroblast transdifferentiation through FBXL16 regulated HIF1α degradation. In general, our findings indicate that miR-1307-5p is important for COPD pathogenesis, and may serve as a potential target for COPD treatment.

Keywords

COPD; FBXL16; HIF1ɑ; Lung fibroblast; Transdifferentiation; miR-1307-5p.

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