Effects Of Deficiency Of The Water Channel AQP4on Bleomycin-induced Lung Fibrosis In Mice

[Background]Idiopathic pulmonary fibrosis is a disease characterized by diffuse alveolitis and alveolar structural disordered and culminating in interstitial pulmonary fibrosis. The disease is progressive and the median survival time after diagnosis is for3years. So far, the pathogenesis of the disease is unknown.Aquaporins are a group of membrane proteins that transport water. There are13subtypes of aquaporins in mammals (AQP0-AQP12). AQP4is distributed in the brain, spinal cord, kidneys, glandular epithelia, skeletal muscle, gastrointestinal tract and airways, and AQP4may participate in many diseases like cerebral edema, seizures, neuromyelitis optica, etc. However, the current research on the role of AQP4in respiratory diseases is fewer; especially the role in pulmonary fibrosis has not been reported.[Objective]To evaluate the role of the water channel AQP4in bleomycin-induced lung fibrosis in mice[Methods]In AQP4gene knockout (AQP4-/-) mice, lung fibrosis was induced by injection of bleomycin (3mg/kg) in to the trachea. The lung coefficient, lung hydroxyproline contents, serum TGF-β1and TNF-α levels were measured. The pathological changes of lung tissues in H-E staining and Masson’s staining were observed.[Results]In the day14after bleomycin-treatment, the lung coefficient values for wild type mice and AQP4-/-mice were1.9-fold and2.3-fold of that of control, respectively; while there was no significant difference between wild type and AQP4-/-mice in the lung coefficient value. The hydroxyproline contents in the lung increased after bleomycin-treatment, in the day28, the lung hydroxyproline contents in wild type and in AQP4-/-mice were1.55-fold and1.4-fold of that in control, respectively; while there was no significant difference between wild type and AQP4-/-mice with bleomycin-induced lung fibrosis in the lung hydroxyproline contents. There was the tendency that the serum TGF-β1and TNF-α level increased in bleomycin-treated mice, however no significant difference was found between wild type and AQP4-/-mice. AQP4-knockout showed no effects on pathological changes of lung tissues in mice with bleomycin-induced lung fibrosis by H-E staining and Masson’s staining.[Conclusion]AQP4might not participate in bleomycin-induced lung fibrosis in mice.