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Altered global microRNA expression in hepatic stellate cells LX-2 by angiotensin-(1-7) and miRNA-1914-5p identification as regulator of pro-fibrogenic elements and lipid metabolism.
de Oliveira da Silva, Brenda; Alberici, Luciane Carla; Ramos, Letícia Ferreira; Silva, Caio Mateus; da Silveira, Marina Bonfogo; Dechant, Carlos R P; Friedman, Scott L; Sakane, Kumiko Koibuchi; Gonçalves, Letícia Rocha; Moraes, Karen C M.
Afiliação
  • de Oliveira da Silva B; Núcleo de Pesquisa em Biologia, Universidade Federal de Ouro Preto, UFOP, Ouro Preto, MG, Brazil; Molecular Biology Laboratory, Department of Biology, Bioscience Institute, Universidade Estadual Paulista "Júlio de Mesquita Filho", UNESP, Rio Claro, SP, Brazil.
  • Alberici LC; Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto, SP, Brazil.
  • Ramos LF; Molecular Biology Laboratory, Department of Biology, Bioscience Institute, Universidade Estadual Paulista "Júlio de Mesquita Filho", UNESP, Rio Claro, SP, Brazil.
  • Silva CM; Molecular Biology Laboratory, Department of Biology, Bioscience Institute, Universidade Estadual Paulista "Júlio de Mesquita Filho", UNESP, Rio Claro, SP, Brazil.
  • da Silveira MB; Molecular Biology Laboratory, Department of Biology, Bioscience Institute, Universidade Estadual Paulista "Júlio de Mesquita Filho", UNESP, Rio Claro, SP, Brazil.
  • Dechant CRP; Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto, SP, Brazil.
  • Friedman SL; Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
  • Sakane KK; Institute of Research and Development of Universidade do Vale do Paraíba, UNIVAP, São José dos Campos, SP, Brazil.
  • Gonçalves LR; Molecular Biology Laboratory, Department of Biology, Bioscience Institute, Universidade Estadual Paulista "Júlio de Mesquita Filho", UNESP, Rio Claro, SP, Brazil.
  • Moraes KCM; Molecular Biology Laboratory, Department of Biology, Bioscience Institute, Universidade Estadual Paulista "Júlio de Mesquita Filho", UNESP, Rio Claro, SP, Brazil. Electronic address: Karenmor@rc.unesp.br.
Int J Biochem Cell Biol ; 98: 137-155, 2018 05.
Article em En | MEDLINE | ID: mdl-29524604
The development of new therapeutic strategies to control or reverse hepatic fibrosis requires thorough knowledge about its molecular and cellular basis. It is known that the heptapeptide angiotensin-(1-7) [ang-(1-7)] can reduce hepatic fibrosis and steatosis in vivo; therefore, it is important to uncover the mechanisms regulating its activity and cellular model of investigation. Ang-(1-7) is a peptide of the renin-angiotensin system (RAS), and here we investigated its modulatory effect on the expression pattern of microRNAs (miRNAs) in hepatic stellate cells (HSCs) LX-2, which transdifferentiate into fibrogenic and proliferative cells. We compared the miRNA profiles between quiesced, activated and ang-(1-7)-treated activated HSCs to identify miRNAs that may regulate their transdifferentiation. Thirteen miRNAs were pointed, and cellular and molecular analyses identified miRNA-1914-5p as a molecule that contributes to the effects of ang-(1-7) on lipid metabolism and on the pro-fibrotic environment control. In our cellular model, we also analyzed the regulators of fatty acid metabolism. Specifically, miRNA-1914-5p regulates the expression of malonyl-CoA decarboxylase (MLYCD) and phosphatidic acid phosphohydrolase (PAP or Lipin-1). Additionally, Lipin-1 was closely correlated with mRNA expression of peroxisome proliferator-activated receptors (PPAR)-α and -γ, which also contribute to lipid homeostasis and to the reduction of TGF-ß1 expression. These findings provide a novel link between RAS and lipid metabolism in controlling HSCs activation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Fibrose / Angiotensina I / Regulação da Expressão Gênica / MicroRNAs / Metabolismo dos Lipídeos / Células Estreladas do Fígado Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Int J Biochem Cell Biol Assunto da revista: BIOQUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Fibrose / Angiotensina I / Regulação da Expressão Gênica / MicroRNAs / Metabolismo dos Lipídeos / Células Estreladas do Fígado Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Int J Biochem Cell Biol Assunto da revista: BIOQUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda