title: High levels of glucose promote the activation of hepatic stellate cells via the p38-mitogen-activated protein kinase signal pathway.
abstract: The relationship between the p38-mitogen-activated protein kinase (p38-MAPK) signal pathway and high glucose-induced hepatic stellate cell (HSC) activation was investigated in this study. Sixty human HSC samples were randomly selected and used in the control (cultured normally), high-glucose (cultured in the presence of high glucose), and blocking (cultured under high-glucose conditions in the presence of the p38-MAPK inhibitor, SB203580) groups. The cells were incubated for 120 h and subsequently analyzed for morphological changes by inverted microscopy and for a-smooth muscle actin (a-SMA) expression (to determine the degree of HSC activation) by the method of streptavidin-biotin complex and western blot. Phospho-p38-MAPK protein expression was analyzed by western blotting. a-SMA and phospho-p38-MAPK expression was significantly upregulated in HSCs cultured under high-glucose conditions, compared to the HSCs cultured normally (P < 0.01). On the other hand, phospho-p38-MAPK and a-SMA protein levels were significantly lower in the blocking group compared to the high-glucose group (P < 0.01). Based on these results, we concluded that high-glucose levels induce HSC activation mediated by phospho-p38-MAPK. Therefore, blocking the p38-MAPK signal pathway could inhibit this effect.
authors.affiliation: The Second Clinical College, Zhejiang TCM University, Gongshu District, Hangzhou, China.
authors.forename: L K
authors.initials: LK
authors.lastname: Wu
authors.affiliation: The Second Clinical College, Zhejiang TCM University, Gongshu District, Hangzhou, China.
authors.forename: Y C
authors.initials: YC
authors.lastname: Liu
authors.affiliation: The Second Clinical College, Zhejiang TCM University, Gongshu District, Hangzhou, China.
authors.forename: G
authors.initials: G
authors.lastname: Ma
authors.affiliation: The Second Clinical College, Zhejiang TCM University, Gongshu District, Hangzhou, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Shi
authors.affiliation: The Second Clinical College, Zhejiang TCM University, Gongshu District, Hangzhou, China wulingkang@163.com.
authors.forename: X M
authors.initials: XM
authors.lastname: He
mesh_terms: D000199:Actins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; C093642:SB 203580