PMID- 20206695
OWN - NLM
STAT- MEDLINE
DCOM- 20101014
LR  - 20100628
IS  - 1878-5492 (Electronic)
IS  - 0966-3274 (Linking)
VI  - 23
IP  - 1-2
DP  - 2010 May
TI  - Prevention of renal interstitial fibrosis via histone deacetylase inhibition in 
      rats with unilateral ureteral obstruction.
PG  - 18-23
LID - 10.1016/j.trim.2010.02.003 [doi]
AB  - 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.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Kinugasa, Fumitaka
AU  - Kinugasa F
AD  - Department of Applied Pharmacology 1, Applied Pharmacology Research Laboratories, 
      Astellas Pharma Inc, Miyukigaoka 21, Tsukuba, Ibaraki 305-8585, Japan. 
      fumitaka.kinugasa@jp.astellas.com
FAU - Noto, Takahisa
AU  - Noto T
FAU - Matsuoka, Hideaki
AU  - Matsuoka H
FAU - Urano, Yasuharu
AU  - Urano Y
FAU - Sudo, Yuji
AU  - Sudo Y
FAU - Takakura, Shoji
AU  - Takakura S
FAU - Mutoh, Seitaro
AU  - Mutoh S
LA  - eng
PT  - Journal Article
DEP - 20100303
PL  - Netherlands
TA  - Transpl Immunol
JT  - Transplant immunology
JID - 9309923
RN  - 0 (Chemokine CCL2)
RN  - 0 (FR276457)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/antagonists & inhibitors/metabolism
MH  - Disease Models, Animal
MH  - Fibrosis/*prevention & control
MH  - Histone Deacetylase Inhibitors/*therapeutic use
MH  - Hydroxamic Acids/*therapeutic use
MH  - Kidney/pathology
MH  - Kidney Transplantation
MH  - Male
MH  - Nephritis, Interstitial/*prevention & control
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ureteral Obstruction/*drug therapy
EDAT- 2010/03/09 06:00
MHDA- 2010/10/15 06:00
CRDT- 2010/03/09 06:00
PHST- 2009/11/16 00:00 [received]
PHST- 2010/01/05 00:00 [revised]
PHST- 2010/02/26 00:00 [accepted]
PHST- 2010/03/09 06:00 [entrez]
PHST- 2010/03/09 06:00 [pubmed]
PHST- 2010/10/15 06:00 [medline]
AID - S0966-3274(10)00014-6 [pii]
AID - 10.1016/j.trim.2010.02.003 [doi]
PST - ppublish
SO  - Transpl Immunol. 2010 May;23(1-2):18-23. doi: 10.1016/j.trim.2010.02.003. Epub 
      2010 Mar 3.