PMID- 19261745
OWN - NLM
STAT- MEDLINE
DCOM- 20090702
LR  - 20220410
IS  - 1931-857X (Print)
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 296
IP  - 5
DP  - 2009 May
TI  - Renal ischemia-reperfusion injury upregulates histone-modifying enzyme systems 
      and alters histone expression at proinflammatory/profibrotic genes.
PG  - F1032-41
LID - 10.1152/ajprenal.00061.2009 [doi]
AB  - Ischemic renal injury can produce chronic renal inflammation and fibrosis. This 
      study tested whether ischemia-reperfusion (I/R) activates histone-modifying 
      enzyme systems and alters histone expression at selected 
      proinflammatory/profibrotic genes. CD-1 mice were subjected to 30 min of 
      unilateral I/R. Contralateral kidneys served as controls. At 1, 3, or 7 days of 
      reflow, bilateral nephrectomy was performed. Renal cortices were probed for 
      monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta1 
      (TGF-beta1), and collagen III mRNAs and cytokine levels. RNA polymerase II (Pol 
      II) binding, which initiates transcription, was quantified at exon 1 of the 
      MCP-1, TGF-beta1, collagen III genes (chromatin immunoprecipitation assay). Two 
      representative gene-activating histone modifications [histone 3 lysine 4 (H3K4) 
      trimethylation (m3) (H3K4m3); histone 2 variant H2A.Z] were sought. Degrees of 
      binding of two relevant histone-modifying enzymes (Set1, BRG1) to target genes 
      were assessed. Renal cortical Set1, BRG1, and H2A.Z mRNAs were measured. Finally, 
      the potential utility of urinary mRNA concentrations as noninvasive markers of 
      these in vivo processes was tested. I/R caused progressive increases in Pol II 
      binding to MCP-1, TGF-beta1, and collagen III genes. Parallel increases in 
      cognate mRNAs also were expressed. Progressive increases in renal cortical Set1, 
      BRG1, H2A.Z mRNAs, and increased Set1/BRG1 binding to target genes occurred. 
      These changes corresponded with: 1) progressive elevations of H3K4m3 and H2A.Z at 
      each test gene; 2) increases in renal cortical TGF-beta1/MCP-1 cytokines; and 3) 
      renal collagen deposition (assessed by histomorphology). Postischemic increases 
      in urinary TGF-beta1, MCP-1, Set1, and BRG1 mRNAs were also observed. We conclude 
      that: 1) I/R upregulates histone-modifying enzyme systems, 2) histone 
      modifications at proinflammatory/profibrotic genes can result, and 3) urinary 
      mRNA assessments may have utility for noninvasive monitoring of these in vivo 
      events.
FAU - Zager, Richard A
AU  - Zager RA
AD  - Department of Medicine, University of Washington, and the Clinical Division, Fred 
      Hutchinson Cancer Research Center, Seattle, Washington, WA 98109, USA. 
      dzager@fhcrc.org
FAU - Johnson, Ali C M
AU  - Johnson AC
LA  - eng
GR  - R0-1-DK-68520/DK/NIDDK NIH HHS/United States
GR  - R37-38432/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090304
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Collagen Type III)
RN  - 0 (Histones)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.7.7.- (RNA Polymerase II)
RN  - EC 3.6.1.- (Smarca4 protein, mouse)
RN  - EC 3.6.4.- (DNA Helicases)
SB  - IM
MH  - Animals
MH  - Biomarkers/urine
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - Collagen Type III/genetics
MH  - DNA Helicases/genetics
MH  - Fibrosis
MH  - Gene Expression Regulation, Enzymologic/*physiology
MH  - Histone-Lysine N-Methyltransferase/genetics
MH  - Histones/*metabolism
MH  - Kidney Cortex/*enzymology/pathology
MH  - Kidney Diseases/genetics/pathology/*physiopathology
MH  - Kidney Tubules, Proximal/cytology/enzymology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Nephritis/genetics/pathology/physiopathology
MH  - Nuclear Proteins/genetics
MH  - RNA Polymerase II/metabolism
MH  - RNA, Messenger/urine
MH  - Reperfusion Injury/genetics/pathology/*physiopathology
MH  - Transcription Factors/genetics
MH  - Transforming Growth Factor beta1/genetics
MH  - Up-Regulation/physiology
PMC - PMC2681356
EDAT- 2009/03/06 09:00
MHDA- 2009/07/03 09:00
PMCR- 2010/05/01
CRDT- 2009/03/06 09:00
PHST- 2009/03/06 09:00 [entrez]
PHST- 2009/03/06 09:00 [pubmed]
PHST- 2009/07/03 09:00 [medline]
PHST- 2010/05/01 00:00 [pmc-release]
AID - 00061.2009 [pii]
AID - F-00061-2009 [pii]
AID - 10.1152/ajprenal.00061.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 May;296(5):F1032-41. doi: 
      10.1152/ajprenal.00061.2009. Epub 2009 Mar 4.