Abstract: SA-PO333

Novel Role of IL-20 Subfamily in the Pathogenesis of CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Pap, Domonkos, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Vannay, Ádám, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Lippai, Rita, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Veres-Székely, Apor, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Rokonay, Réka, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Takács, István Márton, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Sziksz, Erna, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Szebeni, Beáta, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Fekete, Andrea, Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
  • Szabo, Attila J., Semmelweis University, 1st Department of Pediatrics, Budapest, Hungary
Background

Regardless of the etiology kidney fibrosis is a common outcome of progressive kidney diseases. Our recent study showed that levels of interleukin (IL)-20 subfamily members, including IL-19 and IL-24 significantly increased in newborn rat kidneys underwent unilateral ureteral obstruction (UUO). However, their precise role in the pathomechanism of renal fibrosis has not been investigated.

Methods

To study the role of IL-20 cytokine subfamily we applied a mouse model of UUO induced kidney fibrosis on wild type and IL-20 receptor beta gene knockout (IL-20Rβ KO) mice. Masson’s trichrome and Picro-Sirius Red staining, real-time RT-PCR and western blot method were used to investigate the expression of fibrosis associated genes at mRNA and protein level between the two strains. We also investigated the in vitro effect of IL-24 treatment on transforming growth factor beta (TGF-β) and platelet derived growth factor B (PDGF-B) expression of human proximal tubular epithelial (HK-2) cells by real-time RT-PCR and flow cytometry.

Results

We found elevated level of IL-19, IL-24 and IL-20Rβ in the fibrotic kidneys. Lack of IL-20Rβ in KO mice was associated with decreased level of the pro-fibrotic marker alpha smooth muscle actin, TGF-β and PDGF-B expression and also with reduced amount of extracellular matrix deposition in the obstructed kidneys. Treatment of renal epithelial cells with IL-24 increased their TGF-β and PDGF-B production.

Conclusion

Increased expression of IL-19, IL-24 and IL-20Rβ in the fibrotic kidney suggest their role in the pathomechanism of obstructive nephropathy. IL-24 may promote tissue remodeling shifted toward an excessive deposition of extracellular matrix components via increased production of pro-fibrotic factors. Our data suggest that inhibition of IL-24 may have significant anti-fibrotic effect.