Inorganic Nanomaterials as Highly Efficient Inhibitors of Cellular Hepatic Fibrosis.
ACS Appl Mater Interfaces
; 10(38): 31938-31946, 2018 Sep 26.
Article
em En
| MEDLINE
| ID: mdl-30156820
ABSTRACT
Chronic liver dysfunction usually begins with hepatic fibrosis. To date, no effective anti-fibrotic drugs have been approved for clinical use in humans. In the current work, titanium dioxide (TiO2) nanoparticles (NPs) and silicon dioxide (SiO2) NPs are used as active inhibitors with intrinsic chemico-physico properties to block fibrosis and the associated phenotypes through acting on hepatic stellate cells (HSCs, the liver machinery for depositing scar tissues seen in fibrosis). Using LX-2 cells as the HSC model, internalized nanomaterials are found to suppress classical outcomes of cellular fibrosis, for example, inhibiting the expression of collagen I (Col-I) and alpha smooth muscle actin (α-SMA), initiated by transforming growth factor ß (TGF-ß)-activated HSCs in both a concentration-dependent and a time-dependent manner. Biochemically, these nanomaterials could also facilitate the proteolytic breakdown of collagen by up-regulation of matrix metalloproteinases (MMPs) and down-regulation of tissue inhibitors of MMPs (TIMPs). Furthermore, through regulating epithelial-mesenchymal transition (EMT) genes [e.g., E-cadherin (E-Cad) and N-cadherin (N-Cad)], the adhesion and migration profiles of TGF-ß-activated LX-2 cells treated with nanomaterials were further inhibited, reverting them to a more quiescent state. Thus, the collective results pave the new way that nanomaterials can be used as potential therapeutic inhibitors for the treatment of in vivo fibrosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Titânio
/
Dióxido de Silício
/
Nanoestruturas
/
Células Estreladas do Fígado
/
Cirrose Hepática
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Assunto da revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Singapura