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Title: Pressure activates src-dependent FAK-Akt and ERK1/2 signaling pathways in rat hepatic stellate cells
Authors: Wu, H.-J.
Zhang, Z.-Q.
Yu, B.
Liu, S.
Qin, K.-R. 
Zhu, L.
Keywords: Akt
Extracellular signal-regulated kinases 1 and 2
Focal adhesion kinase
Hepatic stellate cells
Issue Date: 2010
Source: Wu, H.-J., Zhang, Z.-Q., Yu, B., Liu, S., Qin, K.-R., Zhu, L. (2010). Pressure activates src-dependent FAK-Akt and ERK1/2 signaling pathways in rat hepatic stellate cells. Cellular Physiology and Biochemistry 26 (3) : 273-280. ScholarBank@NUS Repository.
Abstract: 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 β 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. © 2010 S. Karger AG, Basel.
Source Title: Cellular Physiology and Biochemistry
ISSN: 10158987
DOI: 10.1159/000320583
Appears in Collections:Staff Publications

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