title: Protective role of propofol on the kidney during early unilateral ureteral obstruction through inhibition of epithelial-mesenchymal transition.
abstract: Unilateral ureteral obstruction (UUO) induces functional and pathological changes in the obstructed kidney. Inducible nitric oxide synthase (iNOS) expression is high inearly UUO mouse kidney, which is accompanied with fibrosis. Propofol has preventive effects against renal injury by downregulating iNOS expression in UUO mouse models. However, the role of propofol in kidney fibrosis progression has not been reported. We explored the therapeutic potential and possible mechanisms of action of propofol in kidney fibrosis using a UUO mouse model. Herein, mice anesthetized with propofol or sevoflurane underwent UUO induction. Serum and kidney sections were collected 5 and 28 days post-operation for histological, morphometric, immunofluorescence, microRNA analyses; quantitative PCR and western blotting. In vivo, the effect and mechanism of propofol on epithelial-mesenchymal transition (EMT), transforming growth factor β (TGF-β) signaling and miR-155 levels were detected in cultured HK-2 cells. We found that propofol significantly suppressed UUO-induced kidney fibrosis, which was associated with TGF-β/Smad3 signaling, EMT, and iNOS-NO production. MiR-155 levels were higher in UUO mouse kidneys; compared with sevoflurane, propofol suppressed miR-155 levels. However, in late UUO, propofol could not prevent kidney fibrosis or suppress EMT and miR-155. The in vitro results showed that propofol suppressed TGF-β1-induced EMT by regulating miR-155 levels. As a conclusion, in early UUO mice, propofol may inhibit TGF-β1 expression and NO-iNOS production, consequently inhibiting EMT and kidney fibrosis by regulating miR-155 levels, and might be a new protective agent against kidney injury during surgery and in therapy to prevent kidney fibrosis.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Southwest Medical University Luzhou, Sichuan 646000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Vascular and Thyroid Surgery, Affiliated Hospital of Southwest Medical University Luzhou, Sichuan 646000, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Rehabilitation, Affiliated Hospital of Southwest Medical University Luzhou, Sichuan 646000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Southwest Medical University Luzhou, Sichuan 646000, China.
authors.forename: Xueru
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Vascular and Thyroid Surgery, Affiliated Hospital of Southwest Medical University Luzhou, Sichuan 646000, China.
authors.forename: Yanzheng
authors.initials: Y
authors.lastname: He
keywords: Epithelial-mesenchymal transition (EMT); inducible nitric oxide synthase (iNOS); miR-155; propofol; unilateral ureteral obstruction (UUO)