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Abstract: FR-PO1055

Rubus coreanus Extract Attenuates Kidney Fibrosis Through TGF-β/Smad Pathway Inhibition

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Jin, Wencheng, Seoul National University, Gwanak-gu, Seoul, Korea (the Republic of)
  • Weon, Boram, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
  • Ko, Ara, Seoul National University, Gwanak-gu, Seoul, Korea (the Republic of)
  • Shin, Nayeon, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
  • Lee, Jung Pyo, Seoul National University, Gwanak-gu, Seoul, Korea (the Republic of)
  • Lee, Jeonghwan, Seoul National University, Gwanak-gu, Seoul, Korea (the Republic of)
Background

Rubus coreanus, a wild berry belonging to the Rosaceae genus, has been found to have various health benefits, including anti-oxidative effects.

Methods

Male C57BL/6 mice (7 weeks old, n = 30) were randomly assigned to the sham/vehicle (distilled water), sham/MN705 (600 mg/kg/day), UUO/vehicle, UUO/MN705-low dose (300 mg/kg/day), and UUO/MN705-high dose (600 mg/kg/day) groups in the same numbers (n = 6 in each group). MN705 and distilled water were administered orally using a stainless feeding needle. After 7 days of pre-treatment, sham or UUO operation was performed, and treatment drugs were administered at the same dose for 7 days. In addition, HK-2 cells were cultured and challenged with TGF-β (2 ng/ml) with or without an extract of Rubus coreanus (0.05-0.2 mg/ml).

Results

In the histopathologic specimen of Masson's trichrome stain, areas of kidney interstitial fibrosis were attenuated in the treatment group (3.6 ± 0.9 % area vs. 8.7 ± 3.0 % area, P < 0.01). ). In the Western blot analysis, protein abundance of collagen-1 (50.6% of control, P = 0.04) significantly decreased in the treatment group. In the in vitro experiment, HK-2 cells treated with TGF-β and MN705 showed a dose-dependent significant decrease in the protein expression of fibronectin (64.7% of control in 0.1 mg/ml dose, 22.3% of control in 0.2 mg/ml dose, P = 0.01). and phospho-smad2/3 (87% ± 22% of control in 0.2 mg/ml dose, P < 0.01)

Conclusion

The extract of Rubus coreanus attenuates kidney fibrosis in the UUO mouse model and TGF-β-treated human kidney proximal tubular cells. TGF-β-related Smad and Smurf signaling pathways involved in the development of fibrosis in both in vivo and in vitro models are effectively inhibited through extract of Rubus coreanus and can be a potential target for treatment of kidney fibrosis.