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.
Highlights
To determine whether piceatannol might have a therapeutic effect on renal fibrosis, we administrated vehicle or piceatannol (50 mg/kg/day) to ureteral obstruction (UUO) mice for 2 weeks
HDAC2 and HDAC3 protein expression was unchanged in the UUO kidney (Fig 6C and 6D), whereas that of HDAC8 was decreased in the UUO kidney (Fig 6E). These results indicate that class I histone deacetylase (HDAC) may not play a major role in UUO-induced renal fibrosis
The present study demonstrates that piceatannol attenuates renal fibrosis in a mouse model of UUO
Summary
Results Piceatannol reduces ECM protein and fibrosis marker expression in the UUO kidney No changes in the expression of ECM proteins and fibrosis markers were observed in the control mice treated with piceatannol. Immunofluorescence staining showed that collagen type I expression was increased in the peritubular and periglomerular interstitium in the UUO kidney, which was attenuated by piceatannol treatment (Fig 5B).
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