title: Deficiency of Psgl-1 accelerates bleomycin (BLM)-induced lung fibrosis and inflammation in mice through activating PI3K/AKT.
abstract: 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.
authors.affiliation: Department of Emergency, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Emergency, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, PR China. Electronic address: wangshumingha@foxmail.com.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology; D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003094:Collagen / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015398:Signal Transduction; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology
chemical_list: D000199:Actins; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D020033:Protein Isoforms; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D001761:Bleomycin; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Cytokines; Macrophage; Psgl-1 knockout; Pulmonary fibrosis