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

被引：17

作者：

da Silva, Brenda de Oliveira ^{[1
,3
]}

Alberici, Luciane Carla ^{[2
]}

Ramos, Leticia Ferreira ^{[3
]}

Silva, Caio Mateus ^{[3
]}

da Silveira, Marina Bonfogo ^{[3
]}

Dechant, Carlos R. P. ^{[2
]}

Friedman, Scott L. ^{[4
]}

Sakane, Kumiko Koibuchi ^{[5
]}

Goncalves, Leticia Rocha ^{[3
]}

Moraes, Karen C. M. ^{[3
]}

机构：

[1] Univ Fed Ouro Preto, Nucleo Pesquisa Biol, Ouro Preto, MG, Brazil

[2] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto, SP, Brazil

[3] Univ Estadual Paulista, UNESP, Biosci Inst, Dept Biol,Mol Biol Lab, Rio Claro, SP, Brazil

[4] Mt Sinai Sch Med, Dept Med, Div Liver Dis, New York, NY USA

[5] Univ Vale do Paraiba, UNIVAP, Inst Res & Dev, Sao Jose Dos Campos, SP, Brazil

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2018年 / 98卷

基金：

巴西圣保罗研究基金会;

关键词：

Angiotensin-(1-7); HSC fibrogenesis; Lipid metabolism; MicroRNA; Transdifferentiation; FATTY LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; FIBROSIS; SYSTEM; MECHANISM; GROWTH; DEATH;

D O I：

10.1016/j.biocel.2018.02.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 miRNA1914-5p 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)-alpha and - gamma, which also contribute to lipid homeostasis and to the reduction of TGF-beta 1 expression. These findings provide a novel link between RAS and lipid metabolism in controlling HSCs activation.

引用

页码：137 / 155

页数：19