Induction of heme oxygenase 1 prevents progression of liver fibrosis in Mdr2 knockout mice

被引：65

作者：

Barikbin, Roja ^{[1
]}

Neureiter, Daniel ^{[2
]}

Wirth, Jan ^{[3
]}

Erhardt, Annette ^{[1
]}

Schwinge, Dorothee ^{[3
]}

Kluwe, Johannes ^{[3
]}

Schramm, Christoph ^{[3
]}

Tiegs, Gisa ^{[1
]}

Sass, Gabriele ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Inst Expt Immunol & Hepatol, D-20246 Hamburg, Germany

[2] Paracelsus Private Med Univ, Inst Pathol, Salzburg, Austria

[3] Univ Med Ctr Hamburg Eppendorf, Med Clin 1, D-20246 Hamburg, Germany

来源：

HEPATOLOGY | 2012年 / 55卷 / 02期

关键词：

TUMOR-NECROSIS-FACTOR; ISCHEMIA-REPERFUSION INJURY; P-GLYCOPROTEIN GENE; FACTOR-ALPHA; HOMOZYGOUS DISRUPTION; CARBON-MONOXIDE; DOWN-REGULATION; STELLATE CELLS; CANCER; INFLAMMATION;

D O I：

10.1002/hep.24711

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Induction or overexpression of the heme-degrading enzyme, heme oxygenase 1 (HO-1), has been shown to protect mice from liver damage induced by acute inflammation. We have investigated the effects of HO-1 induction in a mouse model of chronic liver inflammation and fibrogenesis with progression to hepatocellular carcinoma (HCC) (Mdr2ko; FVB.129P2-Abcb4tm1Bor). HO-1 was induced in vivo by treatment with cobalt protoporphyrin IX, starting at week 5 or 12 of mice lifespan, and continued for 7 weeks. Our results showed that HO-1 induction reduced liver damage and chronic inflammation by regulating immune cell infiltration or proliferation as well as tumor necrosis factor receptor signaling. Fibrosis progression was significantly reduced by HO-1 induction in mice with mild, as well as established, portal and lobular fibrosis. HO-1 induction significantly suppressed hepatic stellate cell activation. During established fibrosis, HO-1 induction was able to revert portal inflammation and fibrosis below levels observed at the start of treatment. Moreover, hepatocellular proliferation and signs of dysplasia were decreased after HO-1 induction. Conclusion: Induction of HO-1 interferes with chronic inflammation and fibrogenesis and, in consequence, might delay progression to HCC. (HEPATOLOGY 2012;)

引用

页码：553 / 562

页数：10

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