Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2010-6-28
pubmed:abstractText
Acute rejection following renal transplantation has become manageable with the introduction of calcineurin inhibitors, FK506 and cyclosporine A. However, chronic allograft dysfunction accompanied by renal interstitial fibrosis, which induces graft loss, remains unresolved. Here, we evaluated the effect of FR276457, a pan-histone deacetylase (HDAC) inhibitor, on interstitial fibrosis in the injured kidneys of a rat model of unilateral ureteral obstruction. The injured kidneys, harvested on Day 14 following the operation, showed progression of interstitial fibrosis, increases of hydroxyproline contents, and mRNA expression of collagen type Ialpha1 and monocyte chemotactic protein 1 (MCP-1). However, these changes were found to be prevented with daily oral administration of FR276457. In addition, given that MCP-1 is believed to contribute to progressive fibrosis, we investigated the direct effect of FR276457 on MCP-1 production by activated THP-1 cells in vitro. Results showed that FR276457 administration decreased MCP-1 production in these cells in a concentration-dependent manner. Findings from the present study suggested that a pan-HDAC inhibitor may exert a prophylactic effect against renal interstitial fibrosis by inhibiting MCP-1 production.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1878-5492
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-23
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Prevention of renal interstitial fibrosis via histone deacetylase inhibition in rats with unilateral ureteral obstruction.
pubmed:affiliation
Department of Applied Pharmacology 1, Applied Pharmacology Research Laboratories, Astellas Pharma Inc, Miyukigaoka 21, Tsukuba, Ibaraki 305-8585, Japan. fumitaka.kinugasa@jp.astellas.com
pubmed:publicationType
Journal Article