Exogenous expression of caveolin-1 is sufficient for hepatic stellate cell activation |
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Authors: | Mariana Ilha Ketlen da Silveira Moraes Francieli Rohden Leo Anderson Meira Martins Radovan Borojevic Guido Lenz Florencia Barbé-Tuana Fátima Costa Rodrigues Guma |
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Affiliation: | 1. Programa de Pós-Graduação em Ciências Biológicas- Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre, RS, Brazil;2. Centro de Medicina Regenerativa, Faculdade de Medicina de Petrópolis – FMP, Petrópolis, RJ, Brazil;3. Departamento de Biofísica e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil |
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Abstract: | Caveolin-1 (Cav-1) expression is increased in hepatic stellate cells (HSC) upon liver cirrhosis and it functions as an integral membrane protein of lipid rafts and caveolae that regulates and integrates multiple signals as a platform. This study aimed to evaluate the role of Cav-1 in HSC. Thus, the effects of exogenous expression of Cav-1 in GRX cells, a model of activated HSC, were determined. Here, we demonstrated through evaluating well-known HSC activation markers – such as α-smooth muscle actin, collagen I, and glial fibrillary acidic protein – that up regulation of Cav-1 induced GRX to a more activated phenotype. GRXEGFP-Cav1 presented an increased migration, an altered adhesion pattern, a reorganization f-actin cytoskeleton, an arrested cell cycle, a modified cellular ultrastructure, and a raised endocytic flux. Based on this, GRX EGFP-Cav1 represents a new cellular model that can be an important tool for understanding of events related to HSC activation. Furthermore, our results reinforce the role of Cav-1 as a molecular marker of HSC activation. |
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Keywords: | caveolae caveolin-1 GRX hepatic stellate cells activation liver fibrosis molecular marker |
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