title: Expression of the 78 kD glucose-regulated protein is induced by endoplasmic reticulum stress in the development of hepatopulmonary syndrome.
abstract: OBJECTIVE
  This study is to explore the role of 78 kD glucose-regulated protein (GRP78) in the development of hepatopulmonary syndrome (HPS) in rats.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The increased GRP78 expression is indicative of endoplasmic reticulum stress response during HPS, which may play an important role in the disease pathogenesis.
authors: Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China. Electronic address: zhanghy2001@163.com.
authors: Huiying
authors: H
authors: Zhang
authors: ICU of the Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China.
authors: Minli
authors: M
authors: Lv
authors: Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Jiantao
authors: J
authors: Jia
authors: Institute of Hepatology, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Zhongfu
authors: Z
authors: Zhao
authors: Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Lili
authors: L
authors: Zhang
authors: Pharmacology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Lina
authors: L
authors: Lai
authors: Laboratory of Microbiology and Immunology, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Yanjun
authors: Y
authors: Wu
authors: Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Baohong
authors: B
authors: Li
authors: Physiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Chen
authors: C
authors: Li
authors: Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Jingquan
authors: J
authors: Ji
authors: Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Xiaoxia
authors: X
authors: Tian
authors: Physiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Yan
authors: Y
authors: Liu
authors: Physiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Xujiong
authors: X
authors: Li
authors: Laboratory of Microbiology and Immunology, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Hui
authors: H
authors: Pang
authors: Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
authors: Jianhong
authors: J
authors: Guo
authors: Functional Laboratory, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Limin
authors: L
authors: Wang
authors: Functional Laboratory, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Yimin
authors: Y
authors: Fan
authors: Functional Laboratory, Changzhi Medical College, Changzhi 046000, Shanxi, China.
authors: Cuiying
authors: C
authors: Zhang
authors: Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
authors: Dewu
authors: D
authors: Han
authors: USC Research Center for Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Cheng
authors: C
authors: Ji
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D004731:Endotoxins / Q000097:blood; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D020065:Hepatopulmonary Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000410:Alanine Transaminase; D004731:Endotoxins; D006360:Heat-Shock Proteins; D008315:Malondialdehyde; D014409:Tumor Necrosis Factor-alpha; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP
keywords: 78kD glucose-regulated protein; ALT; CCl(4); ECL; ER; Endoplasmic reticulum stress; GAPDH; GRP78; HPS; Hepatopulmonary syndrome; IETM; Intestinal endotoxemia; Liver cirrhosis; MDA; ROS; TNF-α; alanine transferase; carbon tetrachloride; endoplasmic reticulum; enhanced chemiluminescence; glyceraldehyde-3-phosphate dehydrogenase; hepatopulmonary syndrome; intestinal endotoxemia; malondialdehyde; reactive oxygen species; tumor necrosis factor-α