Rho directs activation-associated changes in rat hepatic stellate cell morphology via regulation of the actin cytoskeleton
✍ Scribed by Hal F. Yee Jr.
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 472 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Hepatic stellate cell activation, thought to play a key role in fibrosis of the liver, is characterized by changes in cellular morphology. The intracellular signals regulating morphological alterations associated with stellate cell activation are uncertain. The ras-like guanosine triphosphatebinding protein, rho, has recently emerged as an important regulator of the actin cytoskeleton, and consequently cell morphology. The aim of this study was to test the hypothesis that rho signaling pathways direct activation-associated morphological changes in stellate cells by regulating the actin cytoskeleton. The morphology and actin cytoskeleton of primary rat hepatic stellate cells were studied with phase contrast, differential interference contrast, and epifluorescence microscopy. Immunohistochemistry and immunoblot analysis were used to examine rho expression and activity, respectively. Quiescent and activated stellate cells were investigated in the absence and presence of C3 transferase, a bacterial toxin that specifically inhibits rho. Stellate cell activation was characterized by the development of prominent intracellular fibers, and the loss of dendrite-like processes and perinuclear retinoid droplets. Moreover, activation was accompanied by the formation of prominent actin stress fibers and focal adhesions. Both rho expression and activity were demonstrated in stellate cells. C3 transferase blocked and reversed, both activation-associated morphological alterations and activation-associated changes in the actin cytoskeleton, in quiescent and activated stellate cells, respectively. These results indicate that rho directs activation-associated changes in rat hepatic stellate cell morphology via regulation of the actin cytoskeleton. (HEPATOLOGY 1998;28:843-850.)
During conditions of chronic liver injury, hepatic stellate cells (i.e., Ito cells, lipocytes) undergo a phenotypic change termed ''activation,'' which is characterized by fibrogenesis, proliferation, and morphological alterations. [1][2][3][4][5] This change Abbreviations: F-actin, filamentous actin; MRLC, myosin II regulatory light chain; PBS, phosphate-buffered solution.