title: Intermediate filaments modulation in an in vitro model of the hepatic stellate cell activation or conversion into the lipocyte phenotype.
abstract: Hepatic stellate cells are intralobular connective tissue cells expressing the myofibroblast or the lipocyte phenotypes. They participate in homeostasis of the liver extracellular matrix, repair, regeneration, and fibrosis under the former phenotype, and control the retinol metabolism, storage, and release under the latter one. They are heterogeneous in terms of their tissue distribution, function, and expression of cytoskeletal proteins. We have studied the expressions of intermediate filaments in the cloned GRX cell line representative of murine hepatic stellate cells, by immunolabeling, reverse transcription polymerase chain reaction (RT-PCR), immunoprecipitation and Western blots. GRX cells expressed vimentin, desmin, glial fibrillary acidic protein (GFAP), and smooth muscle alpha actin (SM-alphaA). Vimentin, desmin, and SMN-alphaA were expressed in all cultures. GFAP showed a heterogeneous intensity of expression and did not form a filamentous cytoskeletal network, showing a distinct punctuate cytoplasmic distribution. When activated by inflammatory mediators, GRX cells increased expression of desmin and GFAP. Retinol-mediated induction of the lipocyte phenotype elicited a strong 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 activated myofibroblast or lipocyte phenotypes with distinct patterns of cytoskeleton structure, metabolic function, and interaction with the tissue environment.
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.lastname: Guma FCR
authors.forename: T G
authors.initials: TG
authors.lastname: Mello
authors.forename: C S
authors.initials: CS
authors.lastname: Mermelstein
authors.forename: V A
authors.initials: VA
authors.lastname: Fortuna
authors.forename: S T
authors.initials: ST
authors.lastname: Wofchuk
authors.forename: C
authors.initials: C
authors.lastname: Gottfried
authors.forename: R M
authors.initials: RM
authors.lastname: Guaragna
authors.forename: M L
authors.initials: ML
authors.lastname: Costa
authors.forename: R
authors.initials: R
authors.lastname: Borojevic
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D003893:Desmin / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014746:Vimentin / Q000378:metabolism
chemical_list: D000199:Actins; D017931:DNA Primers; D003893:Desmin; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D014746:Vimentin