VCAN activates JAK/STAT signaling pathway to promote the progression of LPS-induced acute pneumonia

Background Pneumonia is a lower respiratory tract disease induced by pathogens and is related to the inflammatory stimulation by endotoxin from microorganisms. Objective This study aimed to investigate the effects and potential mechanism of action of versican ( VCAN ) in pneumonia. Methods A mouse model of pneumonia was established using a nasopharyngeal drip containing lipopolysaccharide (LPS). VCAN mRNA and versican protein levels in lung tissues were evaluated by qRT-PCR, western blotting, and immunohistochemistry. Injury and apoptosis in the lung tissue were observed using H&E and TUNEL staining, respectively. The W/D ratio was used to evaluate pulmonary edema. The inflammation levels in the BALF were assayed by ELISA. The signaling pathways regulated by VCAN were analyzed by GSEA. In addition, the role of VCAN in vitro was confirmed in LPS-stimulated ACEs. Cell viability, apoptosis, inflammation, and related proteins were measured by CCK-8 assay, flow cytometry, ELISA, and western blotting, respectively. VCAN mRNA and versican protein levels were significantly increased in the lung tissues of mice with pneumonia. Results VCAN shRNA significantly alleviated pulmonary edema, apoptosis, and lung tissue injury. VCAN shRNA reduced inflammation levels in the BALF. Furthermore, VCAN activated the JAK/STAT signaling pathway. VCAN shRNA markedly suppressed expression of proteins of the JAK/STAT signaling pathway in lung tissues. In addition, VCAN siRNA increased cell viability, decreased apoptosis, reduced inflammation and inhibited the JAK/STAT signaling pathway in LPS-stimulated ACEs. The effect of co-treatment with VCAN siRNA and the JAK1/2 inhibitor ruxolitinib (Rux) on LPS-stimulated ACEs was similar to that of Rux treatment alone. Conclusions VCAN knockdown alleviates lung injury of mice with pneumonia by inhibiting the JAK/STAT signaling pathway.