Advances in medical sciences · 2024
Critical roles of PAI-1 in lipopolysaccharide-induced acute lung injury.
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Li Miao, Song Juan, Tang Xinjun, Bi Jing, Li Yufan, Chen Cuicui, Feng Nana, Song Yuanlin, Wang Linlin
Аннотация
PURPOSE: Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of fibrinolytic systems. The effect of PAI-1 on inflammatory response is still inconsistent. Our study was conducted to investigate its effects on inflammation to clarify the role of PAI-1 in acute lung injury (ALI) induced by lipopolysaccharide (LPS).
MATERIAL AND METHODS: ALI models were established in wild-type (WT) and PAI-1 knockout (KO) mice by LPS intervention for 48 h. Lung histopathology, wet-dry ratio, total cell count and TNF-α concentration in bronchoalveolar lavage fluid (BALF), and inflammation related proteins were detected. Flow cytometry was used to sort neutrophils, macrophages, regulatory T cells (Treg) and T helper cell 17 (Th17). RNA sequencing was performed to find differentially expressed genes. Masson staining and immunohistochemistry were used to analyze pulmonary fiber deposition and proliferation.
RESULTS: Compared with ALI (WT) group, the wet-dry ratio, the total number of BALF cells, the concentration of TNF-α in BALF, and the expression of pp65 in the lung tissue was increased in ALI (PAI-1 KO) group, with increased proportion of neutrophils, decreased proportion of macrophages and decreased proportion of Treg/Th17 in the lung tissue. Collagen fiber deposition and PCNA expression were lighter in ALI (PAI-1 KO) group than ALI (WT) group. PPI analysis showed that PAI-1 was closely related to TNF, IL-6, IL-1β, Smad2/3 and mainly concentrated in the complement and coagulation system, TNF-α and IL-17 signaling pathways.
CONCLUSIONS: PAI-1 KO could aggravate ALI induced by LPS at 48 h. PAI-1 may be an important target to improve the prognosis of ALI.
MATERIAL AND METHODS: ALI models were established in wild-type (WT) and PAI-1 knockout (KO) mice by LPS intervention for 48 h. Lung histopathology, wet-dry ratio, total cell count and TNF-α concentration in bronchoalveolar lavage fluid (BALF), and inflammation related proteins were detected. Flow cytometry was used to sort neutrophils, macrophages, regulatory T cells (Treg) and T helper cell 17 (Th17). RNA sequencing was performed to find differentially expressed genes. Masson staining and immunohistochemistry were used to analyze pulmonary fiber deposition and proliferation.
RESULTS: Compared with ALI (WT) group, the wet-dry ratio, the total number of BALF cells, the concentration of TNF-α in BALF, and the expression of pp65 in the lung tissue was increased in ALI (PAI-1 KO) group, with increased proportion of neutrophils, decreased proportion of macrophages and decreased proportion of Treg/Th17 in the lung tissue. Collagen fiber deposition and PCNA expression were lighter in ALI (PAI-1 KO) group than ALI (WT) group. PPI analysis showed that PAI-1 was closely related to TNF, IL-6, IL-1β, Smad2/3 and mainly concentrated in the complement and coagulation system, TNF-α and IL-17 signaling pathways.
CONCLUSIONS: PAI-1 KO could aggravate ALI induced by LPS at 48 h. PAI-1 may be an important target to improve the prognosis of ALI.