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Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model.

Inoue M, Tazuma S, Kanno K, Hyogo H, Igarashi K, Chayama K - J Clin Biochem Nutr (2010)

Bottom Line: Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH.Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver.These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

ABSTRACT
Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1, a.k.a. HSP-32), which is an inducible enzyme and has anti-oxidation/anti-inflammatory properties shown in various models of organ injuries. Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH. In this study, we investigated the influence of Bach1 ablation in mice on the progression of NASH in methionine-choline deficient (MCD) diet model. Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver. When fed MCD diet, Bach1(-/-) mice exhibited negligible hepatic steatosis compared to pronounced steatohepatitis in wild type mice with 6-fold increase in hepatic triglyceride content. Whereas feeding of MCD diet decreased mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α and microsomal triglyceride transfer protein (MTP) in wild type mice, there were no change in Bach1(-/-) mice. In addition, hepatic concentration of malondialdehyde (MDA), a biomarker for oxidative stress as well as plasma alanine aminotransferase (ALT) was significantly lower in Bach1(-/-) mice. These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

No MeSH data available.


Related in: MedlinePlus

Influence of Bach1−/− ablation on hepatic fibrogenesis. (A) Liver sections from wild type (A and B) and Bach1−/− mice (C and D) fed either regular chow (left panels) or MCD diet (right panels) were processed for Azan-Mallory staining. (original magnification 200×). (B) Following 4 w of either regular chow or MCD diet, hepatic mRNA expressions of αSMA were quantified (n = 5/each group) by quantitative real-time PCR. *p<0.05, regular chow vs MCD diet. †p<0.05, wild type (open bar) vs Bach1−/− mice (closed bar).
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Figure 4: Influence of Bach1−/− ablation on hepatic fibrogenesis. (A) Liver sections from wild type (A and B) and Bach1−/− mice (C and D) fed either regular chow (left panels) or MCD diet (right panels) were processed for Azan-Mallory staining. (original magnification 200×). (B) Following 4 w of either regular chow or MCD diet, hepatic mRNA expressions of αSMA were quantified (n = 5/each group) by quantitative real-time PCR. *p<0.05, regular chow vs MCD diet. †p<0.05, wild type (open bar) vs Bach1−/− mice (closed bar).

Mentions: As previously reported,(23) rodents fed MCD diet develops steatohepatitis mimicking human NASH. Fig. 4A depicts mild pericellular fibrosis with fat deposition in the liver from wild type mice fed MCD diet (upper panel). In contrast, Bach1−/− mice displayed no significant change in the liver (lower panel). Consistent with these morphological changes, hepatic mRNA expression of α smooth muscle actin (αSMA) which is predominantly expressed in activated stellate cells was up-regulated in the liver of wild type mice on MCD diet while it remained unchanged in Bach1−/− mice.


Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model.

Inoue M, Tazuma S, Kanno K, Hyogo H, Igarashi K, Chayama K - J Clin Biochem Nutr (2010)

Influence of Bach1−/− ablation on hepatic fibrogenesis. (A) Liver sections from wild type (A and B) and Bach1−/− mice (C and D) fed either regular chow (left panels) or MCD diet (right panels) were processed for Azan-Mallory staining. (original magnification 200×). (B) Following 4 w of either regular chow or MCD diet, hepatic mRNA expressions of αSMA were quantified (n = 5/each group) by quantitative real-time PCR. *p<0.05, regular chow vs MCD diet. †p<0.05, wild type (open bar) vs Bach1−/− mice (closed bar).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045690&req=5

Figure 4: Influence of Bach1−/− ablation on hepatic fibrogenesis. (A) Liver sections from wild type (A and B) and Bach1−/− mice (C and D) fed either regular chow (left panels) or MCD diet (right panels) were processed for Azan-Mallory staining. (original magnification 200×). (B) Following 4 w of either regular chow or MCD diet, hepatic mRNA expressions of αSMA were quantified (n = 5/each group) by quantitative real-time PCR. *p<0.05, regular chow vs MCD diet. †p<0.05, wild type (open bar) vs Bach1−/− mice (closed bar).
Mentions: As previously reported,(23) rodents fed MCD diet develops steatohepatitis mimicking human NASH. Fig. 4A depicts mild pericellular fibrosis with fat deposition in the liver from wild type mice fed MCD diet (upper panel). In contrast, Bach1−/− mice displayed no significant change in the liver (lower panel). Consistent with these morphological changes, hepatic mRNA expression of α smooth muscle actin (αSMA) which is predominantly expressed in activated stellate cells was up-regulated in the liver of wild type mice on MCD diet while it remained unchanged in Bach1−/− mice.

Bottom Line: Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH.Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver.These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

ABSTRACT
Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1, a.k.a. HSP-32), which is an inducible enzyme and has anti-oxidation/anti-inflammatory properties shown in various models of organ injuries. Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH. In this study, we investigated the influence of Bach1 ablation in mice on the progression of NASH in methionine-choline deficient (MCD) diet model. Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver. When fed MCD diet, Bach1(-/-) mice exhibited negligible hepatic steatosis compared to pronounced steatohepatitis in wild type mice with 6-fold increase in hepatic triglyceride content. Whereas feeding of MCD diet decreased mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α and microsomal triglyceride transfer protein (MTP) in wild type mice, there were no change in Bach1(-/-) mice. In addition, hepatic concentration of malondialdehyde (MDA), a biomarker for oxidative stress as well as plasma alanine aminotransferase (ALT) was significantly lower in Bach1(-/-) mice. These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

No MeSH data available.


Related in: MedlinePlus