title: 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.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Sin Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: The Second Hospital of Jilin University, Changchun, China.
authors.forename: Zhe Hao
authors.initials: ZH
authors.lastname: Piao
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.|Jilin Hospital Affiliated with Jilin University, Jilin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Gwi Ran
authors.initials: GR
authors.lastname: Kim
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Yuhee
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.|Yanbian University Hospital, Jilin Yanbian, China.
authors.forename: Ming Quan
authors.initials: MQ
authors.lastname: Lin
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.|Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005355:Fibrosis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013267:Stilbenes / Q000494:pharmacology*; D014517:Ureteral Obstruction / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D048051:p38 Mitogen-Activated Protein Kinases; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases