AIM: To investigate the relationship between 90-kuD ribosomal S6 kinase (p90RSK) and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro. METHODS: Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy. Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell (HSC) line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chain reaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, then collagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated with or without platelet-derived growth factor (PDGF)-BB at a final concentration of 20 microg/L and the cell growth was determined by MTS conversion. RESULTS: In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significant positive correlation with collagen type I levels. In HSC-T6 cells transfected with RNAi targeted to p90RSK, the expression of collagen type I was down-regulated (61.8% in mRNA, P < 0.01, 89.1% in protein, P < 0.01). However, collagen type I promoter activity was not increased with over-expression of p90RSK and not decreased with low expression either, compared with controls in the same cell line (P = 0.076). Furthermore, p90RSK siRNA exerted the inhibition of HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation. CONCLUSION: p90RSK is over-expressed in activated HSCs and involved in regulating the abnormal expression of collagen type I through initiating the proliferation of HSCs.
AIM: To investigate the relationship between 90-kuD ribosomal S6 kinase (p90RSK) and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro. METHODS:Rathepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy. Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell (HSC) line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chain reaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, then collagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated with or without platelet-derived growth factor (PDGF)-BB at a final concentration of 20 microg/L and the cell growth was determined by MTS conversion. RESULTS: In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significant positive correlation with collagen type I levels. In HSC-T6 cells transfected with RNAi targeted to p90RSK, the expression of collagen type I was down-regulated (61.8% in mRNA, P < 0.01, 89.1% in protein, P < 0.01). However, collagen type I promoter activity was not increased with over-expression of p90RSK and not decreased with low expression either, compared with controls in the same cell line (P = 0.076). Furthermore, p90RSK siRNA exerted the inhibition of HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation. CONCLUSION: p90RSK is over-expressed in activated HSCs and involved in regulating the abnormal expression of collagen type I through initiating the proliferation of HSCs.
Authors: M J Iraburu; J A Domínguez-Rosales; L Fontana; A Auster; E R García-Trevijano; A Covarrubias-Pinedo; A M Rivas-Estilla; P Greenwel; M Rojkind Journal: Hepatology Date: 2000-05 Impact factor: 17.425
Authors: Ganesh R Panta; Swayamjot Kaur; Lakita G Cavin; Maria L Cortés; Frank Mercurio; Leonard Lothstein; Trevor W Sweatman; Mervyn Israel; Marcello Arsura Journal: Mol Cell Biol Date: 2004-03 Impact factor: 4.272
Authors: Oriol Morales-Ibanez; Silvia Affò; Daniel Rodrigo-Torres; Delia Blaya; Cristina Millán; Mar Coll; Luis Perea; Gemma Odena; Thomas Knorpp; Markus F Templin; Montserrat Moreno; José Altamirano; Rosa Miquel; Vicente Arroyo; Pere Ginès; Juan Caballería; Pau Sancho-Bru; Ramon Bataller Journal: Gut Date: 2015-02-04 Impact factor: 23.059