Document Detail

Pressure activates Src-dependent FAK-Akt and ERK1/2 signaling pathways in rat hepatic stellate cells.
MedLine Citation:
PMID:  20798511     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND AIMS: Hepatic fibrosis is associated with elevated sinusoidal pressure, which can be transmitted to the hepatic stellate cells (HSCs) in the perisinusoidal space of Disse. Here, we sought to determine the effects of pressure on cellular growth and Src-dependent signaling pathways in the rat HSCs.
METHODS: Cultured rat HSCs were exposed to pressures (0 to 80 mmHg) by using a pressure-inducing apparatus. The proliferation of the cells was determined by a 5-bromo-2'-deoxy-uridine (BrdU) incorporation assay. Reverse transcription-PCR and Western-blot analysis were used to examine the mRNA and protein levels of representative molecules in Src-dependent signaling pathways.
RESULTS: Pressure at 10 to 20 mmHg applied to the HSCs over 1 h upregulated Brdu incorporation and expression of proliferating cell nuclear antigen (PCNA) and type I collagen, while a higher pressure of 40-80 mmHg did not have noticeable effect. The mRNA level of beta (3) integrin was increased by 1-h application of 5 to 20 mmHg. Immunoblot with phospho-specific antibodies demonstrated the phosphorylation of Src (Tyr418), focal adhesion kinase (FAK) (Tyr397), Akt (Ser473) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (Thr421/Ser424) was increased in response to 10-mmHg pressure. Herbimycin A, an inhibitor of Src phosphorylation, attenuated the pressure-induced HSC proliferation and phosphorylation of above-mentioned signaling molecules.
CONCLUSION: Our data demonstrated that pressure alone induced HSC proliferation involving the activation of Src-dependent signaling pathways.
Han-Jun Wu; Zong-Qi Zhang; Bang Yu; Su Liu; Kai-Rong Qin; Liang Zhu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-25
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  26     ISSN:  1421-9778     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2010  
Date Detail:
Created Date:  2010-08-27     Completed Date:  2010-12-08     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  273-80     Citation Subset:  IM    
Copyright Information:
Copyright 2010 S. Karger AG, Basel.
Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
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MeSH Terms
Benzoquinones / pharmacology
Collagen Type I / metabolism
Enzyme Inhibitors / pharmacology
Focal Adhesion Kinase 1 / metabolism*
Hepatic Stellate Cells / enzymology*,  metabolism
Integrin beta3 / genetics,  metabolism
Lactams, Macrocyclic / pharmacology
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Proliferating Cell Nuclear Antigen / metabolism
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction
src-Family Kinases / antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/Benzoquinones; 0/Collagen Type I; 0/Enzyme Inhibitors; 0/Integrin beta3; 0/Lactams, Macrocyclic; 0/Proliferating Cell Nuclear Antigen; 70563-58-5/herbimycin; EC Adhesion Kinase 1; EC protein, rat; EC Kinases; EC Proteins c-akt; EC Protein Kinase 1; EC Protein Kinase 3

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