Expression of the 78 kD glucose-regulated protein is induced by endoplasmic reticulum stress in the development of hepatopulmonary syndrome |
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| Authors: | Huiying Zhang Minli Lv Jiantao Jia Zhongfu Zhao Lili Zhang Lina Lai Yanjun Wu Baohong Li Chen Li Jingquan Ji Xiaoxia Tian Yan Liu Xujiong Li Hui Pang Jianhong Guo Limin Wang Yimin Fan Cuiying Zhang Dewu Han Cheng Ji |
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| Affiliation: | 1. Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China;2. ICU of the Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China;3. Institute of Hepatology, Changzhi Medical College, Changzhi 046000, Shanxi, China;4. Pharmacology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China;5. Laboratory of Microbiology and Immunology, Changzhi Medical College, Changzhi 046000, Shanxi, China;6. Physiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China;g Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi, China;h Functional Laboratory, Changzhi Medical College, Changzhi 046000, Shanxi, China;i USC Research Center for Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA |
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| Abstract: | ObjectiveThis study is to explore the role of 78 kD glucose-regulated protein (GRP78) in the development of hepatopulmonary syndrome (HPS) in rats.MethodsThe rat model of liver cirrhosis and HPS were induced with multiple pathogenic factors. Hematoxylin and eosin (H & E) staining was performed to detect the pathological changes of the lung and liver tissues. The levels of alanine transferase (ALT), endotoxin, and tumor necrosis factor-α (TNF-α) in plasma and TNF-α and malondialdehyde (MDA) in lung tissues were detected. RT-PCR and Western blotting were conducted to detect the mRNA and protein expression levels of GRP78 in lungs.ResultsThe plasma endotoxin level was gradually increased as HPS developed, and the mRNA and protein expression levels of GRP78 in lungs were also increased as the disease progressed. The levels of ALT and TNF-α in plasma and the contents of TNF-α and MDA in lung tissues were gradually increased along with the disease progression, with a strong positive correlation. Compared with controls, the plasma TNF-α level and the mRNA and protein expression levels of GRP78 in lung tissues were significantly higher in rats with HPS. The levels of endotoxin and ALT in plasma and the level of MDA in lungs were significantly higher in rats with HPS than controls.ConclusionsThe increased GRP78 expression is indicative of endoplasmic reticulum stress response during HPS, which may play an important role in the disease pathogenesis. |
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| Keywords: | HPS, hepatopulmonary syndrome ER, endoplasmic reticulum IETM, intestinal endotoxemia GRP78, 78 kD glucose-regulated protein GAPDH, glyceraldehyde-3-phosphate dehydrogenase ECL, enhanced chemiluminescence ALT, alanine transferase MDA, malondialdehyde TNF-α, tumor necrosis factor-α CCl4, carbon tetrachloride ROS, reactive oxygen species |
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