2. Academic Validation
  3. Telocyte-derived exosomes promote angiogenesis and alleviate acute respiratory distress syndrome via JAK/STAT-miR-221-E2F2 axis

Telocyte-derived exosomes promote angiogenesis and alleviate acute respiratory distress syndrome via JAK/STAT-miR-221-E2F2 axis

  • Mol Biomed. 2025 Apr 8;6(1):21. doi: 10.1186/s43556-025-00259-6.
Rongrong Gao # 1 2,  Xu Zhang # 3 4,  Huihui Ju # 1,  Yile Zhou 1,  Luoyue Yin 1,  Liuke Yang 5,  Pinwen Wu 6,  Xia Sun 7,  Hao Fang 8 9
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2 Clinical Center for Biotherapy at Zhongshan Hospital, Fudan University, Shanghai, China.
  • 3 NHC Key Lab of Reproduction Regulation, Shanghai Engineering Research Center of Reproductive Health Drug and Devices, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.
  • 4 Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.
  • 5 College of Plant Protection, Nanjing Agricultural University, Nanjing, 210000, China.
  • 6 Department of Anesthesiology, Minhang Hospital, Fudan University, Shanghai, China.
  • 7 Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai, China. 18017312998@163.com.
  • 8 Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China. drfanghao@163.com.
  • 9 Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai, China. drfanghao@163.com.
  • # Contributed equally.
PMID: 40198510 DOI: 10.1186/s43556-025-00259-6
Abstract

Acute respiratory distress syndrome (ARDS) is characterized by severe respiratory failure and significant inflammation, leading to vascular and epithelial cell damage. The absence of effective pharmacologic treatments underscores the need for novel therapeutic approaches. Telocytes (TCs), a newly identified type of interstitial cells, have shown potential in tissue repair and angiogenesis, particularly through the release of exosomal MicroRNAs (miRNAs). Exosomes were isolated from LPS (lipopolysaccharide)-stimulated TCs and characterized using western blotting and nanoparticle tracking analysis. The role of exosomal miR-221 in angiogenesis was assessed through tube formation, migration, and proliferation assays in mouse vascular endothelial cells (MVECs). The JAK/STAT pathway's involvement in miR-221 regulation was determined using western blotting and qRT-PCR. A dual-luciferase assay confirmed E2F2 as a direct target of miR-221. ARDS mouse model was established via LPS instillation, and the therapeutic effects of TCs-derived exosomes were evaluated by histopathological scoring, cytokine analysis, and endothelial barrier integrity assays. Our findings demonstrated that exosomes from LPS-stimulated TCs significantly promoted angiogenesis, proliferation, and migration in MVECs. These effects were mediated by miR-221, which downregulated E2F2 expression, an important regulator of endothelial cell functions. The JAK/STAT pathway played a crucial role in miR-221 production, with pathway inhibition reducing miR-221 levels and attenuating its pro-angiogenic effects. In vivo, TCs-derived exosomes reduced lung inflammation and tissue damage in ARDS mice, effects that were reversed by miR-221 inhibition. These results suggested that TCs-derived exosomes promoted angiogenesis and alleviated ARDS through the JAK/STAT-miR-221-E2F2 axis.

Keywords

Acute respiratory distress syndrome; Exosomal microRNA; MiR-221; Telocyte.

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