肺上皮细胞特异性敲除Prtn3减缓博来霉素诱导的小鼠肺纤维化OA

AIM:To investigate the impact of lung epithelial cell-specific knockout of proteinase 3(Prtn3)gene on bleomycin(BLM)-induced pulmonary fibrosis in mice.METHODS:Prtn3-floxed(Prtn3fl/fl)mice were generated using the CRISPR/Cas9 system.Eight to ten-week-old Prtn3fl/fl mice and wild-type(WT)C57BL/6J mice were used(n=10 per group).Lung epithelial cell-specific Prtn3 knockout was induced in Prtn3fl/fl mice via intranasal instillation of AAV6-CMV-Cre.A pulmonary fibrosis model was established by intranasal instillation of BLM at 5 mg/kg.The general condition and body weight changes of the mice were monitored dynamically.At the experimental endpoint,the mice were eutha-nized,and lung tissues were collected for fixation and analysis.Body weight changes,pathological alterations in lung tis-sues,and the levels of fibrosis markers and inflammatory factors were compared between the two groups.RESULTS:Fol-lowing BLM administration,the body weight of the mice decreased in both groups,more significantly in the WT+BLM group.Pathological analysis revealed that lung epithelial cell-specific knockout of Prtn3 significantly alleviated BLM-in-duced inflammatory infiltration(P<0.05)and collagen deposition(P<0.01).Furthermore,the protein expression levels of α-smooth muscle actin,collagen type I alpha 1 chain,fibronectin and transforming growth factor-β1 were significantly decreased(P<0.05 or P<0.01).The expression of macrophage marker F4/80 was also significantly suppressed(P<0.05).CONCLUSION:Lung epithelial cell-specific knockout of Prtn3 effectively attenuates the severity of BLM-induced pulmonary fibrosis in mice.