Figure 1.
TWEAK and its receptor Fn14 are upregulated in ADPKD. Fn14 is upregulated in Pkd1cond/cond;Tam-Cre ADPKD orthologous mice (mutant), Pkd1 inactivated on p10–11. (A) Fn14 gene expression assessed by RT-qPCR in WT (n=6) and mutant kidney samples (n=6) at two different time points, p30 and p45. Gapdh was used as housekeeping control. (B) Fn14 protein level assessed by Western blot in WT (n=6) and mutant kidney samples (n=6) at p30 and p45. Upper panel, densitometry represented as fold change (WT versus mutant) and normalized to GAPDH. Lower panel, representative blots (additional information in Supplemental Figure 1). (C) No significant differences TWEAK cytokine levels were observed in PKD mouse serum by ELISA. (D) Fn14 immunohistochemistry in mouse samples at p30 (WT and mutant) shows specific staining in cyst epithelium (black arrows). Scale bars, 100 µm and 50 µm. Original magnification, ×200 and ×400. (E–G) TWEAK was assessed by ELISA in renal cyst fluid, urine, and plasma from patients with ADPKD and healthy volunteers. (E) TWEAK concentration was higher in most individual samples of ADPKD cyst fluid compared with plasma levels in healthy volunteers. (F) The urinary TWEAK/creatinine (creat) ratio is higher in patients with ADPKD compared with healthy volunteers. (G) No significant differences were observed in plasma TWEAK levels between patients with ADPKD and healthy volunteers. (H) Fn14 immunohistochemistry in human ADPKD shows staining in cyst-lining epithelial cells (arrows). Scale bars, 100 µm and 50 µm. Original magnification, ×400 and ×600. Bars represent means±SEM. *P<0.05, **P<0.01, ***P<0.001.