Fibrinogen links podocyte injury with Toll-like receptor 4 and is associated with disease activity in FSGS patients.
Nephrology (Carlton)
; 23(5): 418-429, 2018 May.
Article
en En
| MEDLINE
| ID: mdl-28407405
ABSTRACT
AIM:
Fibrinogen (Fg) is reported to participate in inflammation through Toll-like receptor 4 (TLR4). However, it remains unknown whether Fg might induce podocyte damage through TLR4 and be related to disease activity in patients with focal segmental glomerulosclerosis (FSGS).METHODS:
We observed Fg-induced alterations in actin and apoptosis in cultured human podocytes transfected with or without TLR4 siRNA. Expression of TLR4, phospho-p38 MAPK and phospho-NF-κB p65 was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blotting, and we analysed urinary Fg levels in adriamycin-treated mice and double immunofluorescence staining for TLR4, Fg and podocin. Urinary Fg changes were also analyzed in FSGS patients under prednisone treatment.RESULTS:
First, Fg dose-dependently induced actin damage and apoptosis in cultured human podocytes, with an Fg-induced increase in TLR4 expression, and TLR4 siRNA transfection prevented these effects. TLR4 knockdown inhibited activation of p38 MAPK and NF-κB p65 in podocytes. Elevated urinary Fg levels were positively correlated with albuminuria in adriamycin-treated mice, in which Fg and TLR4 colocalized and exhibited increased expression in podocytes. Additionally, elevated urinary Fg levels were positively correlated with 24-h proteinuria and foot process width in FSGS patients. Urinary Fg levels were significantly decreased in patients with complete remission but not in those without remission.CONCLUSIONS:
Fg induced podocytes injury via the TLR4-p38 MAPK-NF-κB p65 pathway. In FSGS patients, urinary Fg levels reflect therapeutic response to prednisone and disease activity.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrinógeno
/
Glomeruloesclerosis Focal y Segmentaria
/
Apoptosis
/
Podocitos
/
Receptor Toll-Like 4
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Nephrology (Carlton)
Asunto de la revista:
NEFROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
China