Cellular and molecular effects of silymarin on the transdifferentiation processes of LX-2 cells and its connection with lipid metabolism

Autor(es)

Silva, Caio Mateus ^[1] ; Ferrari, Gustavo Duarte ^[2] ; Alberici, Luciane Carla ^[3] ; Malaspina, Osmar ^[4] ; Moraes, Karen C. M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista, UNESP, Inst Biociencias, Lab Biol Mol, Dept Biol Geral & Aplicada, BR-13506900 Rio Claro, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Ribeirao Preto, SP - Brazil

^[4] Univ Estadual Paulista, UNESP, Inst Biociencias, Ctr Estudos Insetos Sociais, Rio Claro, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Biochemistry; v. 468, n. 1-2 MAR 2020.
• Citações Web of Science: 0

Resumo

Fibrosis process in the liver is a clinical condition established in response to chronic lesions and may be reversible in many situations. In this process, hepatic stellate cells (HSCs) activate and produce extracellular matrix compounds. During fibrosis, the lipid metabolism is also altered and contributes to the transdifferentiation of the HSCs. Thus, controlling lipid metabolism in HSCs is suggested as a method to control or reverse the fibrotic condition. In the search for therapies that modulate lipid metabolism and treat liver diseases, silymarin has been identified as a relevant natural compound to treat liver pathologies. The present study aimed to evaluate the cellular and molecular effects of silymarin in the transdifferentiation process of HSCs (LX-2) from activated phenotype to a more quiesced-like cells , also focusing on understanding the modulatory effects of silymarin on lipid metabolism of HSCs. In our analyses, 100 mu M of silymarin reduced the synthesis of actin filaments in activated cells, the synthesis of the protein level of alpha-SMA, and other pro-fibrotic factors such as CTGF and PFGF. The concentration of 150 mu M silymarin did not reverse the activation aspects of LX-2 cells. However, both evaluated concentrations of the natural compound protected the cells from the negative effects of dimethyl sulfoxide (DMSO). Furthermore, we evaluated lipid-related molecules correlated to the transdifferentiation process of LX-2, and 100 mu M of silymarin demonstrated to control molecules associated with lipid metabolism such as FASN, MLYCD, ACSL4, CPTs, among others. In contrast, cellular incubation with 150 mu M of silymarin increased the synthesis of long-chain fatty acids and triglycerides, regarding the higher presence of DMSO (v/v) in the solvent. In conclusion, silymarin acts as a hepatoprotective agent and modulates the pro-fibrogenic stimuli of LX-2 cells, whose effects depend on stress levels in the cellular environment. (AU)

• Processo FAPESP: 18/05286-3 - Análise mecanístico-funcional do microRNA 1914-5p no processo pró-esteatótico hepático não alcoólico em cultura celular
• Beneficiário: Karen Cristiane Martinez de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/23509-4 - Identificação de miocinas neuroprotetoras liberadas pelo músculo esquelético humano em contração de baixa e alta intensidades: papel da bioenergética mitocondrial e do estresse oxidativo
• Beneficiário: Luciane Carla Alberici
• Modalidade de apoio: Auxílio à Pesquisa - Regular