Intermediate filaments modulation in an in vitro model of the hepatic stellate cell activation or conversion into the lipocyte phenotype

Hepatic stellate cells are intralobular connective tissue cells expressing the myofibroblast or the lipocyte phenotypes. They participate in homeostas is of the liver extracellular matrix, repair, regeneration, and fibrosis un der the former phenotype, and control the retinol metabolism, storage, and release under the latter one. They are heterogeneous in terms of their tiss ue distribution, function, and expression of cytoskeletal proteins. We have studied the expressions of intermediate filaments in the cloned GRX cell l ine representative of murine hepatic stellate cells, by immunolabeling, rev erse transcription polymerase chain reaction (RT-PCR), immunoprecipitation and Western blots. GRX cells expressed vimentin, desmin, glial fibrillary a cidic protein (GFAP), and smooth muscle alpha actin (SM-alphaA). Vimentin, desmin, and SM-alphaA were expressed in all cultures. GFAP showed a heterog eneous intensity of expression and did not form a filamentous cytoskeletal network, showing a distinct punctuate cytoplasmic distribution. When activa ted by inflammatory mediators, GRX cells increased expression of desmin and GFAP. Retinol-mediated induction of the lipocyte phenotype elicited a stro ng decrease of intermediate filament protein expression and the collapse of the filamentous structure of the cytoskeleton. Quiescent hepatic stellate precursors can respond to physiologic or pathologic stimuli, expressing act ivated myofibroblast or lipocyte phenotypes with distinct patterns of cytos keleton structure, metabolic function, and interaction with the tissue envi ronment.