title: Fructose-1,6-bisphosphate induces phenotypic reversion of activated hepatic stellate cell.
abstract: Hepatic stellate cells (HSC) play a key role in liver fibrogenesis. Activation of PPARγ and inhibition of fibrogenic molecules are potential strategies to block HSC activation and differentiation. Aware that the process of hepatic fibrosis involves inflammatory mediators, various anti-inflammatory substances have been studied in an attempt to revert fibrosis. The purpose of this study was to investigate the in vitro effects of fructose-1,6-bisphosphate (FBP) on HSC phenotype reversion. The results demonstrated that FBP induced quiescent phenotype in GRX cells via PPARγ activation. Significant decrease in type I collagen mRNA expression was observed in the first 24h of treatment. These events preceded the reduction of TGF-β1 and total collagen secretion. Thus, FBP promoted downregulation of HSC activation by its antifibrotic action. These findings demonstrate that FBP may have potential as a novel therapeutic agent for the treatment of liver fibrosis.
authors.affiliation: Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre-RS, Brazil.
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: de Mesquita
authors.forename: Shanna
authors.initials: S
authors.lastname: Bitencourt
authors.forename: Eduardo
authors.initials: E
authors.lastname: Caberlon
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: da Silva
authors.forename: Bruno S
authors.initials: BS
authors.lastname: Basso
authors.forename: Julia
authors.initials: J
authors.lastname: Schmid
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Ferreira
authors.forename: Fernanda Dos Santos
authors.initials: Fdos S
authors.lastname: de Oliveira
authors.forename: Jarbas R
authors.initials: JR
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy; D005635:Fructosediphosphates / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D005635:Fructosediphosphates; D047495:PPAR gamma; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; C029063:fructose-1,6-diphosphate
keywords: Fibrosis; Fructose-16-bisphosphate; Hepatic stellate cell; Peroxisome proliferator-activated receptor gamma; Transforming growth factor-beta