Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-Β1-induced inflammatory signaling

Mi Ran Ki; Moon Jung Goo; Jin Kyu Park; Il Hwa Hong; Ae Ri Ji; Seon Young Han; Sang Young You; Eun Mi Lee; Ah Young Kim; Sang Joon Park; Hyun Joo Lee; Shin Yoon Kim; Kyu Shik Jeong

doi:10.1038/labinvest.2010.109

Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-Β1-induced inflammatory signaling

Mi Ran Ki, Moon Jung Goo, Jin Kyu Park, Il Hwa Hong, Ae Ri Ji, Seon Young Han, Sang Young You, Eun Mi Lee, Ah Young Kim, Sang Joon Park, Hyun Joo Lee, Shin Yoon Kim, Kyu Shik Jeong

Kyungpook National University

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

Our earlier report has shown that Helicobacter pylori promoted hepatic fibrosis in a murine model. Herein, in order to elucidate the mechanism by which H. pylori accelerate liver fibrosis, the authors investigated the changes in expression levels of mitogen-activated protein kinases (MAPKs), p53-related proteins, antioxidants, and proinflammatory cytokines in liver samples. H. pylori infection enhanced CCl 4 -induced MAP kinase activation and p53 signaling pathway as well as Bax- and proliferating-cell nuclear antigen expressions, whereas H. pylori alone induced neither of these expressions nor hepatic fibrosis. Moreover, mRNA expressions of inflammatory cytokines, glutathione peroxidase expression, and the proliferative index were strongly augmented in livers of the H. pylori with CCl 4 treatment group compared with those of the CCl 4 -alone treatment group, whereas there was no difference in apoptotic index between the two groups. Interestingly, H. pylori treatment increased the number of α-fetoprotein-expressing hepatocytes independently of CCl 4 intoxication. In vitro analyses, using an immortalized rat hepatic stellate cell (HSC) line, revealed that H. pylori lysates increased the proliferation of HSCs, which was boosted by the addition of transforming growth factor-beta1 (TGF-Β1). Furthermore, the treatment of H. pylori lysates promoted the translocation of nuclear factor kappa-light-chain enhancer of activated B cells (NF-B) into the nucleus based on an increase in the degradation of NF-B inhibitor alpha, in the presence of TGF-Β1, as did H 2 O 2 treatment. In conclusion, H. pylori infection along with an elevated TGF-Β1 may accelerate hepatic fibrosis through increased TGF-Β1-induced pro-inflammatory signaling pathways in HSCs. Moreover, H. pylori infection might increase the risk of TGF-Β1-mediated tumorigenesis by disturbing the balance between apoptosis and proliferation of hepatocytes.

Original language	English
Pages (from-to)	1507-1516
Number of pages	10
Journal	Laboratory Investigation
Volume	90
Issue number	10
DOIs	https://doi.org/10.1038/labinvest.2010.109
State	Published - Oct 2010

Keywords

Helicobacter pylori
TGF-β1
hepatic fibrosis
hepatic stellate cells
inflammation

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10.1038/labinvest.2010.109

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Ki, M. R., Goo, M. J., Park, J. K., Hong, I. H., Ji, A. R., Han, S. Y., You, S. Y., Lee, E. M., Kim, A. Y., Park, S. J., Lee, H. J., Kim, S. Y., & Jeong, K. S. (2010). Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-Β1-induced inflammatory signaling. Laboratory Investigation, 90(10), 1507-1516. https://doi.org/10.1038/labinvest.2010.109

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title = "Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-Β1-induced inflammatory signaling",

abstract = "Our earlier report has shown that Helicobacter pylori promoted hepatic fibrosis in a murine model. Herein, in order to elucidate the mechanism by which H. pylori accelerate liver fibrosis, the authors investigated the changes in expression levels of mitogen-activated protein kinases (MAPKs), p53-related proteins, antioxidants, and proinflammatory cytokines in liver samples. H. pylori infection enhanced CCl 4 -induced MAP kinase activation and p53 signaling pathway as well as Bax- and proliferating-cell nuclear antigen expressions, whereas H. pylori alone induced neither of these expressions nor hepatic fibrosis. Moreover, mRNA expressions of inflammatory cytokines, glutathione peroxidase expression, and the proliferative index were strongly augmented in livers of the H. pylori with CCl 4 treatment group compared with those of the CCl 4 -alone treatment group, whereas there was no difference in apoptotic index between the two groups. Interestingly, H. pylori treatment increased the number of α-fetoprotein-expressing hepatocytes independently of CCl 4 intoxication. In vitro analyses, using an immortalized rat hepatic stellate cell (HSC) line, revealed that H. pylori lysates increased the proliferation of HSCs, which was boosted by the addition of transforming growth factor-beta1 (TGF-Β1). Furthermore, the treatment of H. pylori lysates promoted the translocation of nuclear factor kappa-light-chain enhancer of activated B cells (NF-B) into the nucleus based on an increase in the degradation of NF-B inhibitor alpha, in the presence of TGF-Β1, as did H 2 O 2 treatment. In conclusion, H. pylori infection along with an elevated TGF-Β1 may accelerate hepatic fibrosis through increased TGF-Β1-induced pro-inflammatory signaling pathways in HSCs. Moreover, H. pylori infection might increase the risk of TGF-Β1-mediated tumorigenesis by disturbing the balance between apoptosis and proliferation of hepatocytes.",

keywords = "Helicobacter pylori, TGF-β1, hepatic fibrosis, hepatic stellate cells, inflammation",

author = "Ki, \{Mi Ran\} and Goo, \{Moon Jung\} and Park, \{Jin Kyu\} and Hong, \{Il Hwa\} and Ji, \{Ae Ri\} and Han, \{Seon Young\} and You, \{Sang Young\} and Lee, \{Eun Mi\} and Kim, \{Ah Young\} and Park, \{Sang Joon\} and Lee, \{Hyun Joo\} and Kim, \{Shin Yoon\} and Jeong, \{Kyu Shik\}",

year = "2010",

month = oct,

doi = "10.1038/labinvest.2010.109",

language = "English",

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T1 - Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-Β1-induced inflammatory signaling

AU - Ki, Mi Ran

AU - Goo, Moon Jung

AU - Park, Jin Kyu

AU - Hong, Il Hwa

AU - Ji, Ae Ri

AU - Han, Seon Young

AU - You, Sang Young

AU - Lee, Eun Mi

AU - Kim, Ah Young

AU - Park, Sang Joon

AU - Lee, Hyun Joo

AU - Kim, Shin Yoon

AU - Jeong, Kyu Shik

PY - 2010/10

Y1 - 2010/10

N2 - Our earlier report has shown that Helicobacter pylori promoted hepatic fibrosis in a murine model. Herein, in order to elucidate the mechanism by which H. pylori accelerate liver fibrosis, the authors investigated the changes in expression levels of mitogen-activated protein kinases (MAPKs), p53-related proteins, antioxidants, and proinflammatory cytokines in liver samples. H. pylori infection enhanced CCl 4 -induced MAP kinase activation and p53 signaling pathway as well as Bax- and proliferating-cell nuclear antigen expressions, whereas H. pylori alone induced neither of these expressions nor hepatic fibrosis. Moreover, mRNA expressions of inflammatory cytokines, glutathione peroxidase expression, and the proliferative index were strongly augmented in livers of the H. pylori with CCl 4 treatment group compared with those of the CCl 4 -alone treatment group, whereas there was no difference in apoptotic index between the two groups. Interestingly, H. pylori treatment increased the number of α-fetoprotein-expressing hepatocytes independently of CCl 4 intoxication. In vitro analyses, using an immortalized rat hepatic stellate cell (HSC) line, revealed that H. pylori lysates increased the proliferation of HSCs, which was boosted by the addition of transforming growth factor-beta1 (TGF-Β1). Furthermore, the treatment of H. pylori lysates promoted the translocation of nuclear factor kappa-light-chain enhancer of activated B cells (NF-B) into the nucleus based on an increase in the degradation of NF-B inhibitor alpha, in the presence of TGF-Β1, as did H 2 O 2 treatment. In conclusion, H. pylori infection along with an elevated TGF-Β1 may accelerate hepatic fibrosis through increased TGF-Β1-induced pro-inflammatory signaling pathways in HSCs. Moreover, H. pylori infection might increase the risk of TGF-Β1-mediated tumorigenesis by disturbing the balance between apoptosis and proliferation of hepatocytes.

AB - Our earlier report has shown that Helicobacter pylori promoted hepatic fibrosis in a murine model. Herein, in order to elucidate the mechanism by which H. pylori accelerate liver fibrosis, the authors investigated the changes in expression levels of mitogen-activated protein kinases (MAPKs), p53-related proteins, antioxidants, and proinflammatory cytokines in liver samples. H. pylori infection enhanced CCl 4 -induced MAP kinase activation and p53 signaling pathway as well as Bax- and proliferating-cell nuclear antigen expressions, whereas H. pylori alone induced neither of these expressions nor hepatic fibrosis. Moreover, mRNA expressions of inflammatory cytokines, glutathione peroxidase expression, and the proliferative index were strongly augmented in livers of the H. pylori with CCl 4 treatment group compared with those of the CCl 4 -alone treatment group, whereas there was no difference in apoptotic index between the two groups. Interestingly, H. pylori treatment increased the number of α-fetoprotein-expressing hepatocytes independently of CCl 4 intoxication. In vitro analyses, using an immortalized rat hepatic stellate cell (HSC) line, revealed that H. pylori lysates increased the proliferation of HSCs, which was boosted by the addition of transforming growth factor-beta1 (TGF-Β1). Furthermore, the treatment of H. pylori lysates promoted the translocation of nuclear factor kappa-light-chain enhancer of activated B cells (NF-B) into the nucleus based on an increase in the degradation of NF-B inhibitor alpha, in the presence of TGF-Β1, as did H 2 O 2 treatment. In conclusion, H. pylori infection along with an elevated TGF-Β1 may accelerate hepatic fibrosis through increased TGF-Β1-induced pro-inflammatory signaling pathways in HSCs. Moreover, H. pylori infection might increase the risk of TGF-Β1-mediated tumorigenesis by disturbing the balance between apoptosis and proliferation of hepatocytes.

KW - Helicobacter pylori

KW - TGF-β1

KW - hepatic fibrosis

KW - hepatic stellate cells

KW - inflammation

UR - https://www.scopus.com/pages/publications/77957261598

U2 - 10.1038/labinvest.2010.109

DO - 10.1038/labinvest.2010.109

M3 - Article

C2 - 20531291

AN - SCOPUS:77957261598

SN - 0023-6837

VL - 90

SP - 1507

EP - 1516

JO - Laboratory Investigation

JF - Laboratory Investigation

IS - 10

ER -

Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-Β1-induced inflammatory signaling

Abstract

Keywords

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