Abstract: FR-PO181

Honokiol Decreases UUO-Induced Tubulointerstitial Inflammation and Fibrosis by Regulation of Mitochondrial Sirt3 and Its Dynamics

Session Information

  • Mitochondriacs and More
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Kang, Kyung Pyo, Chonbuk National University Medical School, Jeonju, Jeollabuk-Do, Korea (the Republic of)
  • Park, Woong, Chonbuk National University Medical School, Jeonju, Jeollabuk-Do, Korea (the Republic of)
  • Quan, Yi, Chonbuk National University Medical School, Jeonju, Jeollabuk-Do, Korea (the Republic of)
  • Jang, Jin won, Chonbuk National University Hospital, Jeonju, Korea (the Republic of)
  • Park, Sung Kwang, Chonbuk National University Medical School, Jeonju, Jeollabuk-Do, Korea (the Republic of)
  • Kim, Won, Chonbuk National University Medical School, Jeonju, Jeollabuk-Do, Korea (the Republic of)
Background

Sirt3 is a NAD+-dependent deacetylase in mitochondria, which has a role of maintain the mitochondrial function by deacetylation. Sirt3 might protect the cells from reactive oxygen species, apoptosis, and mitochondrial dynamics. In progressive renal disease, tubulointerstitial fibrosis is a final common feature, which is characterized by inflammation, excessive extracellular matrix deposition and organ dysfunction. Honokiol is a natural biphenolic compound derived from the bark of magnolia trees and known as an activator of sirt3 in murine cardiomyopathy model. In this study, we investigate the protective effect of honokiol on unilateral ureteral obstruction (UUO)-induced tubulointerstitial inflammation and fibrosis by regulation of mitochondrial Sirt3.

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-SMA, type I collagen were performed. We also evaluated cell adhesion molecule expression, mitochondrial dynamics and TGF-β1/Smad signaling pathway after ureteral obstruction.

Results

Renal tubular injury and fibrosis were increased after ureteral obstruction. After treatment of honokiol, renal tubular injury and fibrosis were significantly decreased. The number of α-SMA positive fibroblasts and F4/80 positive macrophages were significantly decreased after honokiol treatment in UUO kidney. In Western blot analysis, type I collagen and intercellular adhesion molecule (ICAM)-1 expression was decreased after honokiol treatment in UUO kidney. Sirt3 expression was significantly decreased after UUO surgery, however, honokiol treatment recovered Sirt3 expression in UUO kidney. Mitochondrial fission, as shown Drp1 expression, was increased afer ureteral obstruction, however, honokiol treatment decreased UUO-induced increases of Drp1 expression. In contrast, mitochondrial fusion, as shown OPA1 expression, was decreased after ureteral obstruction and honokiol treatment was recovered.

Conclusion

These results suggest that honokiol has a beneficial effect on UUO-induced tubulointersitial inflammation and fibrosis by regulation of mitochondrial sirt3 and its dynamics.

Funding

  • Government Support - Non-U.S.