Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients
Liver fibrosis induces intrahepatic microcirculation disorder and hypoxic stress. Hypoxic stress has the potential for an increase in the possibility of more liver fibrosis and carcinogenesis. Liver biopsy is a standard method that evaluates of intrahepatic hypoxia, however, is invasive and has a ri...
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doaj-c6a715874fe445d98fd0fcfa9ffa931d2021-09-17T04:36:58ZengElsevierBiochemistry and Biophysics Reports2405-58082021-09-0127101068Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patientsAkifumi Kuwano0Masatake Tanaka1Hideo Suzuki2Miho Kurokawa3Koji Imoto4Shigeki Tashiro5Takeshi Goya6Motoyuki Kohjima7Masaki Kato8Yoshihiro Ogawa9Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Department of Hepatology, Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Corresponding author.Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; CREST, Japan Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, JapanLiver fibrosis induces intrahepatic microcirculation disorder and hypoxic stress. Hypoxic stress has the potential for an increase in the possibility of more liver fibrosis and carcinogenesis. Liver biopsy is a standard method that evaluates of intrahepatic hypoxia, however, is invasive and has a risk of bleeding as a complication. Here, we investigated the hypoxia reactive gene expressions in peripheral blood mononuclear cells (PBMC) from chronic liver disease patients to evaluate intrahepatic hypoxia in a non-invasive manner. The subjects enrolled for this study were composed of 20 healthy volunteers (HV) and 48 patients with chronic liver disease (CLD). CLD patients contained 24 patients with chronic hepatitis(CH)and 24 patients with liver cirrhosis (LC). PBMC were isolated from heparinized peripheral blood samples. We measured the transcriptional expression of hypoxia reactive genes and inflammatory cytokines by quantitative RT-PCR. mRNA expression of adrenomedullin (AM), vascular endothelial growth factor A (VEGFA) superoxide dismutase (SOD), glutathione peroxidase (GPx) (p < 0.05), Interleukin-6 (IL-6), transforming growth factor-beta (TGF-β) and heme oxygenase-1 (HO-1) in CLD group were significantly higher than HV. AM mRNA expression is correlated with serum lactate dehydrogenase (LDH), serum albumin (Alb), IL6, and SOD mRNA expression. The hypoxia reactive gene expression in PBMCs from CLD patients was more upregulated than HV. Especially, angiogenic genes were notably upregulated and correlated with liver fibrosis. Here, we suggest that mRNA expression of AM in PBMCs could be the biomarker of intrahepatic hypoxia.http://www.sciencedirect.com/science/article/pii/S240558082100162XAdrenomedullinChronic liver diseaseIntrahepatic hypoxiaPeripheral blood mononuclear cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Akifumi Kuwano Masatake Tanaka Hideo Suzuki Miho Kurokawa Koji Imoto Shigeki Tashiro Takeshi Goya Motoyuki Kohjima Masaki Kato Yoshihiro Ogawa |
spellingShingle |
Akifumi Kuwano Masatake Tanaka Hideo Suzuki Miho Kurokawa Koji Imoto Shigeki Tashiro Takeshi Goya Motoyuki Kohjima Masaki Kato Yoshihiro Ogawa Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients Biochemistry and Biophysics Reports Adrenomedullin Chronic liver disease Intrahepatic hypoxia Peripheral blood mononuclear cells |
author_facet |
Akifumi Kuwano Masatake Tanaka Hideo Suzuki Miho Kurokawa Koji Imoto Shigeki Tashiro Takeshi Goya Motoyuki Kohjima Masaki Kato Yoshihiro Ogawa |
author_sort |
Akifumi Kuwano |
title |
Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients |
title_short |
Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients |
title_full |
Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients |
title_fullStr |
Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients |
title_full_unstemmed |
Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients |
title_sort |
upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients |
publisher |
Elsevier |
series |
Biochemistry and Biophysics Reports |
issn |
2405-5808 |
publishDate |
2021-09-01 |
description |
Liver fibrosis induces intrahepatic microcirculation disorder and hypoxic stress. Hypoxic stress has the potential for an increase in the possibility of more liver fibrosis and carcinogenesis. Liver biopsy is a standard method that evaluates of intrahepatic hypoxia, however, is invasive and has a risk of bleeding as a complication. Here, we investigated the hypoxia reactive gene expressions in peripheral blood mononuclear cells (PBMC) from chronic liver disease patients to evaluate intrahepatic hypoxia in a non-invasive manner. The subjects enrolled for this study were composed of 20 healthy volunteers (HV) and 48 patients with chronic liver disease (CLD). CLD patients contained 24 patients with chronic hepatitis(CH)and 24 patients with liver cirrhosis (LC). PBMC were isolated from heparinized peripheral blood samples. We measured the transcriptional expression of hypoxia reactive genes and inflammatory cytokines by quantitative RT-PCR. mRNA expression of adrenomedullin (AM), vascular endothelial growth factor A (VEGFA) superoxide dismutase (SOD), glutathione peroxidase (GPx) (p < 0.05), Interleukin-6 (IL-6), transforming growth factor-beta (TGF-β) and heme oxygenase-1 (HO-1) in CLD group were significantly higher than HV. AM mRNA expression is correlated with serum lactate dehydrogenase (LDH), serum albumin (Alb), IL6, and SOD mRNA expression. The hypoxia reactive gene expression in PBMCs from CLD patients was more upregulated than HV. Especially, angiogenic genes were notably upregulated and correlated with liver fibrosis. Here, we suggest that mRNA expression of AM in PBMCs could be the biomarker of intrahepatic hypoxia. |
topic |
Adrenomedullin Chronic liver disease Intrahepatic hypoxia Peripheral blood mononuclear cells |
url |
http://www.sciencedirect.com/science/article/pii/S240558082100162X |
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