Abstract: TH-PO285

Interleukin-10 Alleviates Ureteral Obstruction-Induced Renal Fibrosis by Reduction of Inflammation, Oxidative Stress, and Endoplasmic Reticulum Stress

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Author

  • Jung, Kyong-Jin, Yeungnam University College of Medicine, Nam-gu, Daejeon, Korea (the Republic of)
Background

Imbalance of oxidative stress, endoplasmic reticulum (ER) stressand accumulation of extracellular matrix results in renal fibrosis contributes to progressive renal failure. Recent studies suggested that interleukin (IL)-10 plays potent impacts on the fibrosis-related immunomodulation.However, the role of IL-10 against unilateral ureteral obstruction (UUO)-induced ER stress remains poorly understood.

Methods

Here, we investigated the mechanisms of IL-10 on ER stress-induced renal fibrosis by UUO model in IL-10 knockout (KO) mice and a normal kidney cell line (TMCK-1). Age-matched 10 weeks old male IL-10 KO mice and wild-type (WT) mice were divided into control (CON) and UUO groups. The mice were sacrificed at 3 days or 7 days after UUO. ER stress and profibrotic protein levels were evaluated by,western blotting. Periodic acid Schiff and Masson's trichrome stain were used for analyzed histologic changes and collagen deposition.To evaluate oxidative stress levels checked production of O2-, H2O2,malondihydrogenase and expression of 4-HNE. To investigate correlation among the IL-10, CHOP and α-SMA expression, immunofluorescence staining was used.In vitro, treatment of ER stress inducer (tunicamycin, thapsigargin and brefeldin A)with or without transfected siRNA (IL-10and CHOP) or CHOP overexpression in TMCK-1 cells.

Results

In this study, we found IL-10 KO UUO mice promoted renal fibrosis by more excessive tubular damage (tubular dilatation, cast formation andtubular cells infiltration), collagen deposition and oxidative stress production. We also confirmed IL-10 KO mice express higher level of profibrotic genes (α-SMA, COL1 and FN) and ER stress genes (GRP78/Bip and CHOP) after UUO. We observed IL-10, CHOP and α-SMA were highly expressed in tubulointerstitial lesion of UUO mice than CON mice. In vitro, transient depletion of CHOP attenuated expression of profibrotic genes.

Conclusion

Present study shows that IL-10 protecting was opposed to ER stress mediated-renal fibrosis. Combination of IL-10 and ER stress therapy could be a strong protective effect for patients with chronic kidney diseases.