Interaction of CD80 with Neph1: a potential mechanism of podocyte injury.
Clin Exp Nephrol
; 22(3): 508-516, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-29022109
ABSTRACT
BACKGROUND:
The induction of CD80 on podocytes has been shown in animal models of podocyte injury and in certain cases of nephrotic syndrome. In a lipopolysaccharide (LPS)-induced mouse model of albuminuria, we have recently shown a signalling axis of LPS-myeloid cell activation-TNFα production-podocyte CD80 induction-albuminuria. Therefore, in this report, we investigated the cellular and molecular consequences of TNFα addition and CD80 expression on cultured podocytes.METHODS:
A murine podocyte cell line was used for TNFα treatment and for over-expressing CD80. Expression and localization of various podocyte proteins was analysed by reverse transcriptase-polymerase chain reaction, western blotting and immunofluorescence. HEK293 cells were used to biochemically characterize interactions.RESULTS:
Podocytes treated with LPS in vitro did not cause CD80 upregulation but TNFα treatment was associated with an increase in CD80 levels, actin derangement and poor wound healing. Podocytes stably expressing CD80 showed actin derangement and co-localization with Neph1. CD80 and Neph1 interaction was confirmed by pull down assays of CD80 and Neph1 transfected in HEK293 cells.CONCLUSION:
Addition of TNFα to podocytes causes CD80 upregulation, actin reorganization and podocyte injury. Overexpressed CD80 and Neph1 interact via their extracellular domain. This interaction implies a mechanism of slit diaphragm disruption and possible use of small molecules that disrupt CD80-Neph1 interaction as a potential for treatment of nephrotic syndrome associated with CD80 upregulation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Necrose Tumoral alfa
/
Antígeno B7-1
/
Podócitos
/
Proteínas de Membrana
/
Síndrome Nefrótica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Clin Exp Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Índia
País de publicação:
JAPAN
/
JAPON
/
JAPÃO
/
JP