Send to

Choose Destination
Nephrology (Carlton). 2018 May;23(5):418-429. doi: 10.1111/nep.13046.

Fibrinogen links podocyte injury with Toll-like receptor 4 and is associated with disease activity in FSGS patients.

Author information

Division of Nephrology, Jinling Hospital, Southern Medical University, Nanjing, China.
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.



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).


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.


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.


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.


Toll-like receptor 4; fibrinogen; focal segmental glomerulosclerosis; inflammation; podocyte

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center