Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPARγ and NF-κB

Hui Yang, Long Feng Zhao, Z. Zhao, Yan Wang, Jing Jing Zhao, Li Zhang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

AIM: 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). CONCLUSION: 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.

Original languageEnglish
Pages (from-to)1680-1688
Number of pages9
JournalWorld Journal of Gastroenterology
Volume18
Issue number14
DOIs
Publication statusPublished - 2012

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Heme Oxygenase-1
NF-kappa B
PPAR gamma
Liver Cirrhosis
Liver
Fibrosis
Hemin
Hydroxyproline
Aspartate Aminotransferases
Alanine Transaminase
Real-Time Polymerase Chain Reaction
Serum
Acids
Collagen Type IV
Wounds and Injuries
Smooth Muscle
Wistar Rats
Actins
Albumins
Collagen

Keywords

  • Heme oxygenase-1
  • Hemin
  • Liver fibrosis
  • Nuclear factor-kappa B
  • Peroxisome proliferator-activated receptor gamma

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPARγ and NF-κB. / Yang, Hui; Zhao, Long Feng; Zhao, Z.; Wang, Yan; Zhao, Jing Jing; Zhang, Li.

In: World Journal of Gastroenterology, Vol. 18, No. 14, 2012, p. 1680-1688.

Research output: Contribution to journalArticle

Yang, Hui ; Zhao, Long Feng ; Zhao, Z. ; Wang, Yan ; Zhao, Jing Jing ; Zhang, Li. / Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPARγ and NF-κB. In: World Journal of Gastroenterology. 2012 ; Vol. 18, No. 14. pp. 1680-1688.
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abstract = "AIM: 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). CONCLUSION: 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.",
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author = "Hui Yang and Zhao, {Long Feng} and Z. Zhao and Yan Wang and Zhao, {Jing Jing} and Li Zhang",
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TY - JOUR

T1 - Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPARγ and NF-κB

AU - Yang, Hui

AU - Zhao, Long Feng

AU - Zhao, Z.

AU - Wang, Yan

AU - Zhao, Jing Jing

AU - Zhang, Li

PY - 2012

Y1 - 2012

N2 - AIM: 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). CONCLUSION: 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.

AB - AIM: 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). CONCLUSION: 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.

KW - Heme oxygenase-1

KW - Hemin

KW - Liver fibrosis

KW - Nuclear factor-kappa B

KW - Peroxisome proliferator-activated receptor gamma

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