{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T13:23:17Z","timestamp":1775913797033,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T00:00:00Z","timestamp":1196899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ethanol may cause an increase in sinusoidal pressure accompanied by portal hypertension. Hepatic stellate cells (HSCs) located in hepatic sinusoids may therefore be frequently exposed to dual stimulations of mechanical pressure and ethanol exposure in alcoholic liver injury. In this study, the effects of pressure loading and ethanol exposure on activation of rat cultured HSCs were investigated using an in vitro pressure\u2010inducing apparatus. HSCs were cultured in media containing ethanol (0\u2013100 mM) under different pressures (1\u201340 mmHg). Morphological changes and migration index were determined. We also determined the expression levels of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and mitogen\u2010activated protein kinases (MAPKs) by Western blot analysis and the level of collagen IV and transforming growth factor \u03b21 (TGF\u2010\u03b21) by ELISA. Pressure loading alone induced up\u2010regulation of \u03b1\u2010SMA via the extracellular signal\u2010regulated kinases 1 and 2 (ERK1\/2) and c\u2010jun N\u2010terminal kinase (JNK) signaling pathways, prolonged extension of marginal length, and increased production of collagen IV. In contrast, ethanol exposure alone increased only extension of marginal length and cell migration. Dual stimulations of pressure loading and ethanol exposure enhanced the production of TGF\u2010\u03b21 and migration index. The TGF\u2010\u03b21\u2010dependent p38 MAPK pathway may operate for production of extracellular matrix (ECM) or enhanced migration in the case of dual stimulations. In conclusion, static pressure loading is an important factor directly accelerating the activation of HSCs. Although increased sinusoidal pressure and ethanol exposure might differentially modulate HSC activation, both stimuli are involved in an additive manner in some situations. J. Cell. Physiol. 215: 472\u2013480, 2008. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21329","type":"journal-article","created":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T17:22:51Z","timestamp":1196961771000},"page":"472-480","source":"Crossref","is-referenced-by-count":14,"title":["Pressure loading and ethanol exposure differentially modulate rat hepatic stellate cell 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