CXXC5 Attenuates Pulmonary Fibrosis in a Bleomycin-Induced Mouse Model and MLFs by Suppression of the CD40/CD40L Pathway.

ABSTRACT: Objective:To investigate the role of CXXC5 and the CD40/CD40L pathway in lung fibrosis. Methods:(1) We constructed mouse models of bleomycin-induced pulmonary fibrosis and transfected them with a CXXC5 overexpression vector to evaluate the severity of pulmonary fibrosis. (2) Mouse lung fibroblast (MLF) models stably overexpressed or knockout of CXXC5 vector were constructed. After transforming growth factor-?1 (TGF-?1) stimulation, we examined the proliferation and apoptosis of the MLF model and evaluated the expression of mesenchymal markers and the CXXC5/CD40/CD40L pathway. Results:(1) Compared with other groups, the overexpressed CXXC5 group had less alveolar structure destruction, thinner alveolar septum, and lower Ashcroft score. (2) In bleomycin-induced mice, the expression of CD40 and CD40L increased at both transcriptional and protein levels, and the same changes were observed in ?-smooth muscle actin (?-SMA) and collagen type I (Colla I). After upregulation of CXXC5, the increase in CD40, CD40L, ?-SMA, and Colla I was attenuated. (3) Stimulated with TGF-?1, MLF proliferation was activated, apoptosis was suppressed, and the expression of CD40, CD40L, ?-SMA, and Colla I was increased at both transcriptional and protein levels. After upregulation of CXXC5, these changes were attenuated. Conclusion:CXXC5 inhibits pulmonary fibrosis and transformation to myofibroblasts by negative feedback regulation of the CD40/CD40L pathway.

SUBMITTER: Cheng W 

PROVIDER: S-EPMC7160725 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature