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Abstract: SA-PO124

TRPC3, a Key Target in Cisplatin-Induced Renal Fibrosis

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Najem, Hinda, Universite Saint-Joseph, Beirut, Lebanon
  • Hajal, Joelle, Universite Saint-Joseph, Beirut, Lebanon
  • Saliba, Youakim, Universite Saint-Joseph, Beirut, Lebanon
  • Fares, Nassim, Universite Saint-Joseph, Beirut, Lebanon
Background

Cisplatin (Cisp) is a chemotherapy drug that induces renal cellular lesions with excessive accumulation of extracellular matrix leading to renal fibrosis. Transient receptor potential canonical channels type 3 (TRPC3) are non-selective Ca2+ channels strongly implicated in cardio-renal diseases. We previously demonstrated the role of TRPC3 in renal fibrosis of obstructive origins. Herein, we evaluate TRPC3 implication in renal toxicity mediated by Cisplatin.

Methods

34 adult male C57BL/6 mice were divided into four groups: WT Sham (n=8), WT Cisp (n=8), KO Sham (n=9), and KO Cisp (n=9). Cisp was administered by intraperitoneal injections (7mg.kg-1, one injection per week) for four weeks. Kidney tissues, blood, and urine samples were harvested for histological and biochemical studies.

Results

KO Cisp mice showed a decrease in urinary albumin/creatinine ratio, associated with a reduction of fibrotic TGF-β/SMADs and NFATc3 pathways compared to WT. Moreover, kidneys of KO Cisp mice showed a significant alleviation in apoptosis and oxidative DNA damage, as well as a reduction of Tcf21+/PDGFRα+ activated fibroblasts.

Conclusion

TRPC3 channels seem to play a substantial role in cisplatin-induced renal fibrosis. TRPC3 might constitute a key therapeutic target for improving renal remodeling in cisplatin chemotherapy.

Funding

  • Private Foundation Support