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

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.