title: Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPARγ and NF-κB.
abstract: OBJECTIVE
  To investigate the effects of heme oxygenase (HO)-1 on liver fibrosis and the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor-kappa B (NF-κB) in rats.
  
  
  METHODS
  Sixty Wistar rats were used to construct liver fibrosis models and were randomly divided into 5 groups: group A (normal, untreated), group B (model for 4 wk, untreated), group C (model for 6 wk, untreated), group D [model for 6 wk, treated with zinc protoporphyrin IX (ZnPP-IX) from week 4 to week 6], group E (model for 6 wk, treated with hemin from week 4 to week 6). Next, liver injury was assessed by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin levels. The degree of hepatic fibrosis was evaluated by measuring serum hyaluronate acid (HA), type IV collagen (IV-C) and by histological examination. Hydroxyproline (Hyp) content in the liver homogenate was determined. The expression levels of alpha-smooth muscle actin (α-SMA) in liver tissue were measured by real-time quantitative polymerase chain reaction (RT-PCR). The expression levels of PPARγ and NF-κB were determined by RT-PCR and Western blotting.
  
  
  RESULTS
  The expression of HO-1 increased with the development of fibrosis. Induction of HO-1 by hemin significantly attenuated the severity of liver injury and the levels of liver fibrosis as compared with inhibition of HO-1 by ZnPP-IX. The concentrations of serum ALT, AST, HA and IV-C in group E decreased compared with group C and group D (P < 0.01). Amount of Hyp and α-SMA in the liver tissues in group E decreased compared with group C (0.62 ± 0.14 vs 0.84 ± 0.07, 1.42 ± 0.17 vs 1.84 ± 0.17, respectively, P < 0.01) and group D (0.62 ± 0.14 vs 1.11 ± 0.16, 1.42 ± 0.17 vs 2.56 ± 0.37, respectively, P < 0.01). The expression of PPARγ at levels of transcription and translation decreased with the development of fibrosis especially in group D; and it increased in group E compared with groups C and D (0.88 ± 0.15 vs 0.56 ± 0.19, 0.88 ± 0.15 vs 0.41 ± 0.11, respectively, P < 0.01). The expression of NF-κB increased with the development of fibrosis especially in group D; and it decreased in group E compared with groups C and D (1.43 ± 0.31 vs 1.89 ± 0.29, 1.43 ± 0.31 vs 2.53 ± 0.54, respectively, P < 0.01).
  
  
  CONCLUSIONS
  Our data demonstrate a potential mechanism that HO-1 can prevent liver fibrosis by enhancing the expression of PPARγ and decreasing the expression of NF-κB in liver tissues.
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Long-Feng
authors.initials: LF
authors.lastname: Zhao
authors.forename: Zhong-Fu
authors.initials: ZF
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016328:NF-kappa B; D047495:PPAR gamma; D011524:Protoporphyrins; D012333:RNA, Messenger; C017803:zinc protoporphyrin; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat