Hepatitis B Virus X Protein Reduces Podocyte Adhesion via Downregulation of α3ß1 Integrin.
Cell Physiol Biochem
; 41(2): 689-700, 2017.
Article
em En
| MEDLINE
| ID: mdl-28214836
ABSTRACT
BACKGROUND/AIMS:
Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) is characterized by a reduced number of podocytes due to apoptosis and shedding from the basement membrane. However, the pathological mechanism of HBV-GN is unclear. We previously showed that hepatitis B virus X protein (HBx) promotes apoptosis in tubular epithelial cells. In this study, we transfected podocytes with HBx and examined the effects on adhesion and apoptosis of these cells.METHODS:
Podocytes were transfected with pc-DNA3.1 (+)-HBx. One control group was not transfected and another control group was transfected with empty plasmids. Podocyte adhesion was assessed by a fluorescence assay, apoptosis was measured by flow cytometry and fluorescence microscopy, and expression of α3ß1 integrin was determined by western blotting and the reverse transcription polymerase chain reaction (RT-PCR). Activity of caspase-8 was measured by a spectrophotometric assay.RESULTS:
Relative to controls, podocytes with pc-DNA3.1(+)-HBx had reduced cell adhesion, increased apoptosis, reduced expression of α3ß1 integrin, and increased caspase-8 activity. ß1 integrin blockage reduced podocyte adhesion, but increased apoptosis and caspase-8 activity. Treatment of transfected podocytes with a caspase-8 inhibitor (Z-IETD-FMK) had no effect on the HBx-mediated integrin downregulation and reduced podocyte adhesion, suggesting that α3ß1 integrin downregulaton is sufficient to alter cell adhesion.CONCLUSIONS:
Our in vitro results indicate that HBx reduced podocyte adhesion and expression of α3ß1 integrin, and increased apoptosis. Moreover, HBx-mediated downregulation of α3ß1 integrin expression is sufficient to reduce podocyte adhesion. HBx-induced apoptosis of podocytes may contribute to HBV-GN.Palavras-chave
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transativadores
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Physiol Biochem
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article