2. Academic Validation
  3. MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence

MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence

  • Respir Res. 2024 Feb 5;25(1):67. doi: 10.1186/s12931-024-02696-3.
Fang Lu # 1,  Li-Peng Yao # 2 3,  Dan-Dan Gao # 2 4,  Tahereh Alinejad # 5 6,  Xin-Qing Jiang 7,  Qi Wu 4,  Qiao-Cheng Zhai 4,  Ming Liu 4,  Sheng-Mei Zhu 4,  Mao-Xiang Qian 4 8,  Li-Feng Xu 9,  Cheng-Shui Chen 10 11,  Feng Zhang 12
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China.
  • 2 Wenzhou Medical University, Wenzhou, 325035, China.
  • 3 Ningbo College of Health Sciences, Ningbo, 315000, China.
  • 4 Joint Innovation Center for Engineering in Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China.
  • 5 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.
  • 6 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325015, China.
  • 7 Zhejiang Chinese Medical University the 2 nd Clinical Medical College, Hangzhou, 310053, China.
  • 8 Institute of Pediatrics, Department of Hematology and Oncology, Institutes of Biomedical Sciences, National Children's Medical Center, Children's Hospital of Fudan University, Fudan University, Shanghai, 200032, China.
  • 9 Joint Innovation Center for Engineering in Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China. qz1109@wmu.edu.cn.
  • 10 Department of Respiratory and Critical Care, 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 Joint Innovation Center for Engineering in Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China. fengzhang@wmu.edu.cn.
  • # Contributed equally.
PMID: 38317146 DOI: 10.1186/s12931-024-02696-3
Abstract

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.

Keywords

COPD; Lung fibroblast; Senescence; ZFP36L1; miR-377-3p.

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