Deficiency of Psgl-1 accelerates bleomycin (BLM)-induced lung fibrosis and inflammation in mice through activating PI3K/AKT.

Pulmonary fibrosis is a disease characterized by unremitting fibrosis accumulation in the lung, causing respiratory failure eventually. Presently, the immunological mechanism underlying pulmonary fibrosis still remains unclear. P-selectin glycoprotein ligand-1 (Psgl-1) is a leukocyte ligand that regulates recruitment and activation of multiple cell types, which is associated with phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway activation. In the present study, we attempted to clarify the AKT activation induced by Psgl-1 knockout in mice with bleomycin (BLM)-induced pulmonary fibrosis. The findings indicated that after BLM induction, myeloid Psgl-1-deficient mice exhibited enhanced transforming growth factor-β 1 (TGF-β1), α-SMA and various Collagen accumulation in comparison to the wild type mice, resulting in accelerated morbidity and declined survival rate. Further, Psgl-1-knockout mice showed decreased number of macrophages and T-cells responding to BLM treatment after assays of the alveolar lavage and cell composition in the lung. Notably, abnormal macrophage polarization was observed in Psgl-1-deficient mice, accompanied with enhanced cytokines secretion after BLM induction. The findings here possibly referred to an uncontrollable wound healing related to Psgl-1 knockout, which modulates inflammatory response and macrophage phenotypes, leading to fibrosis enhancement ultimately. However, further experiments are still necessary to characterize the precise molecular mechanism of Psgl-1 in mice fibrosis.