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Abstract: TH-PO915

Honokiol decreases TGF-β1 Induced Renal Fibroblast Activation by Regulation of TGF-β1/Smad Signaling Pathway

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Park, Woong, Chonbuk National University Medical School, Jeonju, Korea (the Republic of)
  • Kim, Won, Chonbuk National University Medical School, Jeonju, Korea (the Republic of)
  • Kang, Kyung Pyo, Chonbuk National University Medical School, Jeonju, Korea (the Republic of)
Background

In progressive renal disease, tubulointerstitial fibrosis is a final common feature. These fibrotic process is characterized by inflammation, excessive extracellular matrix deposition and organ dysfunction. Modulation of renal fibrogenesis may be one of the promising therapeutic targets for attenuating the progression of chronic kidney diseases. Honokiol is a natural biphenolic compound derived from the bark of magnolia trees and has anti-inflammatory, anti-oxidative, anti-tumor and neuroprotective effects. In this study, we investigate the effect of honokiol on TGF-β1-induced real fibroblast activation and unilateral ureteral obstruction (UUO)-induced renal fibrosis.

Methods

Renal fibrosis was induced by UUO in the six-week-old C57BL/6 mice for 10 days. Honokiol (5 mg/kg) was treated by intraperitoneal injection for 7 days before induction of renal fibrosis and continued for 10 days. Histologic examination and Western blot analysis for α-smooth muscle actin (α-SMA), type I collagen and intercellular adhesion molecule (ICAM)-1 were performed. In vitro experiments were performed using rat renal fibroblast cell line (NRK-49F cells). Cell proliferation and migration were evaluated by XTT assay and wound healing assay. TGF-β1-induced renal fibroblast activation was evaluated by Western blot analysis.

Results

Treatment of TGF-β1 increased significantly proliferation and cell migration of NRK-49F cells compared to that of vehicle treated cells. Honokiol treatment decreased TGF-β1-induced renal fibroblast proliferation and activation in a dose dependent manner. TGF-β1 treatment increased the levels of phospho-Smad2 and 3 in NRK-49F cells, and honokiol significantly decreased the levels of phosphorylation of Smad2 and 3. In in vivo experiment, honokiol decreased UUO-induced renal tubular injury and renal fibrosis. Honokiol also decreased UUO-induced renal inflammation by regulation of phosphorylation of NFκB p65.

Conclusion

These results suggest that honokiol has a beneficial effect on UUO-induced tubulointersitial inflammation and fibrosis by regulation of TGF-β1/Smad signaling pathway.

Funding

  • Government Support - Non-U.S.