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Peer-reviewedCC BY-NC-NDRespiratory research

Deleted in lymphocytic leukemia 2 contributes to lung fibroblast activation and pulmonary fibrosis by interacting with and triggering focal adhesion kinase phosphorylation.

  • Honglan Zhu1,2
  • Junjie Lan3
  • Xiao Wu4
  • Ya Gao5
  • Xingfen Ran6
  • Runrun He6
  • Zhixiang Luo6
  • Yiju Cheng7,8
  • Zifeng Yang9,10,11
  • Daishun Liu12,13
13 affiliations
  1. 1Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550002, P.R. China.
  2. 2Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases, Guiyang, Guizhou, 550002, P.R. China.
  3. 3Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550002, P.R. China.
  4. 4Department of Critical Care Medicine, The Second People's Hospital of Guiyang, Guiyang, Guizhou, 550002, P.R. China.
  5. 5The Fifth Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, Zunyi, Guizhou, 563000, P.R. China.
  6. 6Department of Clinical Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, P.R. China.
  7. 7Department of Respiratory and Critical Care Medicine, The Fourth People's Hospital of Guiyang, Guiyang, Guizhou, 550002, P.R. China. [email protected].
  8. 8Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550002, P.R. China. [email protected].
  9. 9State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510230, P.R. China. [email protected].
  10. 10Guangzhou Laboratory, Guangzhou, Guangdong, 510000, P.R. China. [email protected].
  11. 11State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau (SAR), 519020, P.R. China. [email protected].
  12. 12Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550002, P.R. China. [email protected].
  13. 13Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases, Guiyang, Guizhou, 550002, P.R. China. [email protected].
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Abstract

The etiology of idiopathic pulmonary fibrosis (IPF) remains unknown, and therapeutic interventions are currently restricted. The activation of lung fibroblasts and the focal adhesion kinase (FAK) signaling pathway are crucial to the pathogenesis of IPF, yet the exact molecular mechanisms remain incompletely understood. Our study shows that the deleted in lymphocytic leukemia 2 (DLEU2) is elevated in the peripheral blood of patients with IPF, as well as in the lung tissues of mice with pulmonary fibrosis. Functional assays revealed that overexpression of DLEU2 facilitated fibrogenesis, whereas its suppression attenuated lung fibrosis in vivo and impeded fibroblast activation in vitro, predominantly through the regulation of FAK phosphorylation. Mechanistically, our findings reveal that DLEU2 regulates lung fibroblast activation by targeting miR-29a-3p. Conversely, inhibition of miR-29a-3p reversed the anti-fibrotic effects observed upon DLEU2 knockdown. Furthermore, DLEU2 was shown to directly interact with FAK, enhancing its phosphorylation and thereby facilitating fibrogenesis; inhibition of FAK phosphorylation counteracted the pro-fibrotic effects induced by DLEU2 overexpression. Taken together, these findings clarify the function of DLEU2 in facilitating FAK phosphorylation via its interactions with miR-29a-3p and FAK. The findings of this study suggest that DLEU2 may serve as a novel diagnostic biomarker and a potential therapeutic target for the treatment of IPF.

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Cite

BibTeXRIS
BibTeX
@article{zhu2026deleted,
  title = {{Deleted in lymphocytic leukemia 2 contributes to lung fibroblast activation and pulmonary fibrosis by interacting with and triggering focal adhesion kinase phosphorylation.}},
  author = {Honglan Zhu and Junjie Lan and Xiao Wu and Ya Gao and Xingfen Ran and Runrun He and Zhixiang Luo and Yiju Cheng and Zifeng Yang and Daishun Liu},
  journal = {Respiratory research},
  year = {2026},
  month = jul,
  doi = {10.1186/s12931-026-03841-w},
  url = {https://europepmc.org/article/MED/42902263},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Deleted in lymphocytic leukemia 2 contributes to lung fibroblast activation and pulmonary fibrosis by interacting with and triggering focal adhesion kinase phosphorylation.
AU  - Honglan Zhu
AU  - Junjie Lan
AU  - Xiao Wu
AU  - Ya Gao
AU  - Xingfen Ran
AU  - Runrun He
AU  - Zhixiang Luo
AU  - Yiju Cheng
AU  - Zifeng Yang
AU  - Daishun Liu
PY  - 2026
DA  - 2026/07/01
JO  - Respiratory research
DO  - 10.1186/s12931-026-03841-w
UR  - https://europepmc.org/article/MED/42902263
AB  - The etiology of idiopathic pulmonary fibrosis (IPF) remains unknown, and therapeutic interventions are currently restricted. The activation of lung fibroblasts and the focal adhesion kinase (FAK) signaling pathway are crucial to the pathogenesis of IPF, yet the exact molecular mechanisms remain incompletely understood. Our study shows that the deleted in lymphocytic leukemia 2 (DLEU2) is elevated in the peripheral blood of patients with IPF, as well as in the lung tissues of mice with pulmonary fibrosis. Functional assays revealed that overexpression of DLEU2 facilitated fibrogenesis, whereas its suppression attenuated lung fibrosis in vivo and impeded fibroblast activation in vitro, predominantly through the regulation of FAK phosphorylation. Mechanistically, our findings reveal that DLEU2 regulates lung fibroblast activation by targeting miR-29a-3p. Conversely, inhibition of miR-29a-3p reversed the anti-fibrotic effects observed upon DLEU2 knockdown. Furthermore, DLEU2 was shown to directly interact with FAK, enhancing its phosphorylation and thereby facilitating fibrogenesis; inhibition of FAK phosphorylation counteracted the pro-fibrotic effects induced by DLEU2 overexpression. Taken together, these findings clarify the function of DLEU2 in facilitating FAK phosphorylation via its interactions with miR-29a-3p and FAK. The findings of this study suggest that DLEU2 may serve as a novel diagnostic biomarker and a potential therapeutic target for the treatment of IPF.
SN  - 1465-9921
SN  - 1465-993X
ER  -