High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase

Rie Sugimoto, Munechika Enjoji, Motoyuki Kohjima, Satoshi Tsuruta, Marie Fukushima, Masataka Iwao, Toshiyo Sonta, Kazuhiro Kotoh, Toyoshi Inoguchi, Makoto Nakamuta

研究成果: ジャーナルへの寄稿記事

76 引用 (Scopus)

抄録

Background: Nonalcoholic steatohepatitis is a clinicopathologic condition that may progress to liver fibrosis. Hyperglycemia is supposed to be one of the factors inducing hepatic fibrogenesis, but the mechanism has not been fully clarified. Oxidative stress is increasingly found in patients with diabetes/hyperglycemia in which conditions reactive oxygen species (ROS) are produced. Methods: We performed experiments using hepatic stellate cells (HSCs) in culture in order to confirm the effect of high glucose concentrations on cell proliferation, type I collagen production, ROS production and activation of mitogen-activated protein (MAP) kinase pathway. Results: High glucose stimulated cell growth of HSCs and upregulated the levels of activated/phosphorylated extracellular signal-regulated kinase 1/2 and free radical production in HSCs. The MAP kinase phosphorylation and cell proliferation were suppressed by diphenylene iodonium chloride, an NADPH oxidase inhibitor, and by calphostin C, a protein kinase C (PKC)-specific inhibitor. Increased type I collagen mRNA and protein levels were also observed in HSCs at high glucose concentrations. Conclusions: Our findings indicate that high glucose concentrations may stimulate ROS production through PKC-dependent activation of NADPH oxidase, and induce MAP kinase phosphorylation subsequent to proliferation and type I collagen production by HSCs.

元の言語英語
ページ(範囲)1018-1026
ページ数9
ジャーナルLiver International
25
発行部数5
DOI
出版物ステータス出版済み - 10 1 2005

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Hepatic Stellate Cells
Mitogen-Activated Protein Kinases
Free Radicals
Collagen
Glucose
Collagen Type I
Reactive Oxygen Species
NADPH Oxidase
Hyperglycemia
Protein Kinase C
Phosphorylation
Cell Proliferation
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Liver Cirrhosis
Chlorides
Oxidative Stress
Cell Culture Techniques
Messenger RNA
Liver

All Science Journal Classification (ASJC) codes

  • Hepatology

これを引用

High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase. / Sugimoto, Rie; Enjoji, Munechika; Kohjima, Motoyuki; Tsuruta, Satoshi; Fukushima, Marie; Iwao, Masataka; Sonta, Toshiyo; Kotoh, Kazuhiro; Inoguchi, Toyoshi; Nakamuta, Makoto.

:: Liver International, 巻 25, 番号 5, 01.10.2005, p. 1018-1026.

研究成果: ジャーナルへの寄稿記事

Sugimoto, Rie ; Enjoji, Munechika ; Kohjima, Motoyuki ; Tsuruta, Satoshi ; Fukushima, Marie ; Iwao, Masataka ; Sonta, Toshiyo ; Kotoh, Kazuhiro ; Inoguchi, Toyoshi ; Nakamuta, Makoto. / High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase. :: Liver International. 2005 ; 巻 25, 番号 5. pp. 1018-1026.
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author = "Rie Sugimoto and Munechika Enjoji and Motoyuki Kohjima and Satoshi Tsuruta and Marie Fukushima and Masataka Iwao and Toshiyo Sonta and Kazuhiro Kotoh and Toyoshi Inoguchi and Makoto Nakamuta",
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T1 - High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase

AU - Sugimoto, Rie

AU - Enjoji, Munechika

AU - Kohjima, Motoyuki

AU - Tsuruta, Satoshi

AU - Fukushima, Marie

AU - Iwao, Masataka

AU - Sonta, Toshiyo

AU - Kotoh, Kazuhiro

AU - Inoguchi, Toyoshi

AU - Nakamuta, Makoto

PY - 2005/10/1

Y1 - 2005/10/1

N2 - Background: Nonalcoholic steatohepatitis is a clinicopathologic condition that may progress to liver fibrosis. Hyperglycemia is supposed to be one of the factors inducing hepatic fibrogenesis, but the mechanism has not been fully clarified. Oxidative stress is increasingly found in patients with diabetes/hyperglycemia in which conditions reactive oxygen species (ROS) are produced. Methods: We performed experiments using hepatic stellate cells (HSCs) in culture in order to confirm the effect of high glucose concentrations on cell proliferation, type I collagen production, ROS production and activation of mitogen-activated protein (MAP) kinase pathway. Results: High glucose stimulated cell growth of HSCs and upregulated the levels of activated/phosphorylated extracellular signal-regulated kinase 1/2 and free radical production in HSCs. The MAP kinase phosphorylation and cell proliferation were suppressed by diphenylene iodonium chloride, an NADPH oxidase inhibitor, and by calphostin C, a protein kinase C (PKC)-specific inhibitor. Increased type I collagen mRNA and protein levels were also observed in HSCs at high glucose concentrations. Conclusions: Our findings indicate that high glucose concentrations may stimulate ROS production through PKC-dependent activation of NADPH oxidase, and induce MAP kinase phosphorylation subsequent to proliferation and type I collagen production by HSCs.

AB - Background: Nonalcoholic steatohepatitis is a clinicopathologic condition that may progress to liver fibrosis. Hyperglycemia is supposed to be one of the factors inducing hepatic fibrogenesis, but the mechanism has not been fully clarified. Oxidative stress is increasingly found in patients with diabetes/hyperglycemia in which conditions reactive oxygen species (ROS) are produced. Methods: We performed experiments using hepatic stellate cells (HSCs) in culture in order to confirm the effect of high glucose concentrations on cell proliferation, type I collagen production, ROS production and activation of mitogen-activated protein (MAP) kinase pathway. Results: High glucose stimulated cell growth of HSCs and upregulated the levels of activated/phosphorylated extracellular signal-regulated kinase 1/2 and free radical production in HSCs. The MAP kinase phosphorylation and cell proliferation were suppressed by diphenylene iodonium chloride, an NADPH oxidase inhibitor, and by calphostin C, a protein kinase C (PKC)-specific inhibitor. Increased type I collagen mRNA and protein levels were also observed in HSCs at high glucose concentrations. Conclusions: Our findings indicate that high glucose concentrations may stimulate ROS production through PKC-dependent activation of NADPH oxidase, and induce MAP kinase phosphorylation subsequent to proliferation and type I collagen production by HSCs.

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