Piceatannol Attenuates Renal Fibrosis Induced by Unilateral Ureteral Obstruction via Downregulation of Histone Deacetylase 4/5 or p38-MAPK Signaling.

Abstract

Piceatannol, a resveratrol metabolite, is a phenolic compound found in red wine and grapes. We investigated the effect of piceatannol on renal fibrosis and histone deacetylase (HDAC) expression in a mouse model of unilateral ureteral obstruction (UUO). Fibrosis was established by UUO and piceatannol was intraperitoneally injected for 2 weeks. Piceatannol suppressed extracellular matrix (ECM) protein deposition including collagen type I and fibronectin as well as connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in UUO kidneys. However, the expressions of epithelial-mesenchymal transition (EMT) marker genes, such as N-cadherin and E-cadherin, were not changed in the kidneys after UUO. Masson's trichrome staining and fluorescence immunostaining showed that piceatannol administration attenuated collagen deposition in UUO kidneys. HDAC1, HDAC4, HDAC5, HDAC6, and HDAC10 protein expression was upregulated in UUO kidneys, whereas that of HDAC8 was downregulated. Piceatannol treatment significantly reduced HDAC4 and HDAC5 protein expression. Further, piceatannol attenuated phosphorylation of p38 mitogen-activated protein kinase (p38-MAPK) in UUO kidneys, but not that of transforming growth factor beta1-Smad2/3. These results suggest that class I HDACs and class IIa/b HDACs are involved in renal fibrosis development. Piceatannol may be a beneficial therapeutic agent for treating renal fibrosis via reduction of HDAC4 and HDAC5 protein expression or suppression of the p38-MAPK signaling pathway.

• Authors: Sin Young Choi, Zhe Hao Piao, Li Jin, Jung Ha Kim, Gwi Ran Kim, Yuhee Ryu, Ming Quan Lin, Hyung-Seok Kim, Hae Jin Kee, Myung Ho Jeong
• Journal: PloS one (PLoS One) Vol. 11 Issue 11 Pg. e0167340 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27902771 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Extracellular Matrix Proteins
• Stilbenes
• 3,3',4,5'-tetrahydroxystilbene
• p38 Mitogen-Activated Protein Kinases
• Hdac5 protein, mouse
• Histone Deacetylases

Topics

• Animals
• Biomarkers (metabolism)
• Down-Regulation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Extracellular Matrix Proteins (metabolism)
• Fibrosis
• Gene Expression Regulation, Enzymologic (drug effects)
• Histone Deacetylases (metabolism)
• Kidney (drug effects, pathology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Stilbenes (pharmacology)
• Ureteral Obstruction (genetics, metabolism, pathology)
• p38 Mitogen-Activated Protein Kinases (metabolism)