title: Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction.
abstract: Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases. Many studies have demonstrated that heme oxygenase-1 (HO-1) is involved in diverse biological processes as a cytoprotective molecule, including anti-inflammatory, anti-oxidant, anti-apoptotic, antiproliferative, and immunomodulatory effects. However, the mechanisms of HO-1 prevention in renal interstitial fibrosis remain unknown. In this study, HO-1 transgenic (TG) mice were employed to investigate the effect of HO-1 on renal fibrosis using a unilateral ureter obstruction (UUO) model and to explore the potential mechanisms. We found that HO-1 was adaptively upregulated in kidneys of both TG and wild type (WT) mice after UUO. The levels of HO-1 mRNA and protein were increased in TG mice compared with WT mice under normal conditions. HO-1 expression was further enhanced after UUO and remained high during the entire experimental process. Renal interstitial fibrosis in the TG group was significantly attenuated compared with that in the WT group after UUO. Moreover, overexpression of HO-1 inhibited the loss of peritubular capillaries. In addition, UUO-induced activation and proliferation of myofibroblasts were suppressed by HO-1 overexpression. Furthermore, HO-1 restrained tubulointerstitial infiltration of macrophages and regulated the secretion of inflammatory cytokines in UUO mice. We also found that high expression of HO-1 inhibited reactivation of Wnt/β-catenin signaling, which could play a crucial role in attenuating renal fibrosis. In conclusion, these data suggest that HO-1 prevents renal tubulointerstitial fibrosis possibly by regulating the inflammatory response and Wnt/β-catenin signaling. This study provides evidence that augmentation of HO-1 levels may be a therapeutic strategy against renal interstitial fibrosis.
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Wei
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jian-Si
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Qing-Fang
authors.initials: QF
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yu-Xiao
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shi-Lei
authors.initials: SL
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Qiu-Ju
authors.initials: QJ
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Lv
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics*; D051379:Mice; D058628:Myofibroblasts / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000209:etiology* / Q000473:pathology*; D015854:Up-Regulation; D014517:Ureteral Obstruction / Q000150:complications*; D060449:Wnt Signaling Pathway
chemical_list: D051547:Heme Oxygenase-1