PMID- 20555348
OWN - NLM
STAT- MEDLINE
DCOM- 20101008
LR  - 20221207
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 130
IP  - 10
DP  - 2010 Oct
TI  - Epigenetically altered wound healing in keloid fibroblasts.
PG  - 2489-96
LID - 10.1038/jid.2010.162 [doi]
AB  - Keloids are benign dermal tumors that form during wound healing in genetically 
      susceptible individuals. The mechanism(s) of keloid formation is unknown and 
      there is no satisfactory treatment. We have reported differences between 
      fibroblasts cultured from normal scars and keloids that include a pattern of 
      glucocorticoid resistance and altered regulation of genes in several signaling 
      pathways associated with fibrosis, including Wnt and IGF/IGF-binding protein 5 
      (IGFBP5). As previously reported for glucocorticoid resistance, decreased 
      expression of the Wnt inhibitor secreted frizzled-related protein 1 (SFRP1), 
      matrix metalloproteinase 3 (MMP3), and dermatopontin (DPT), and increased 
      expression of IGFBP5 and jagged 1 (JAG1) are seen only in fibroblasts cultured 
      from the keloid nodule. In vivo, decreased expression of SFRP1 and SFRP2 and 
      increased expression of IGFBP5 proteins are observed only in proliferative keloid 
      tissue. There is no consistent difference in the replicative life span of normal 
      and keloid fibroblasts, and the altered response to hydrocortisone (HC) and 
      differential regulation of a subset of genes in standard culture medium are 
      maintained throughout at least 80% of the culture lifetime. Preliminary studies 
      using ChIP-chip analysis, Trichostatin A, and 5-aza-2'-deoxycytidine further 
      support an epigenetically altered program in keloid fibroblasts that includes an 
      altered pattern of DNA methylation and histone acetylation.
FAU - Russell, Shirley B
AU  - Russell SB
AD  - Center for Human Genetics Research and Department of Medicine, Vanderbilt 
      University School of Medicine, Nashville, Tennessee 37232, USA. 
      shirley.b.russell@vanderbilt.edu
FAU - Russell, James D
AU  - Russell JD
FAU - Trupin, Kathryn M
AU  - Trupin KM
FAU - Gayden, Angela E
AU  - Gayden AE
FAU - Opalenik, Susan R
AU  - Opalenik SR
FAU - Nanney, Lillian B
AU  - Nanney LB
FAU - Broquist, Alan H
AU  - Broquist AH
FAU - Raju, Latha
AU  - Raju L
FAU - Williams, Scott M
AU  - Williams SM
LA  - eng
GR  - 1UL1RR024975/RR/NCRR NIH HHS/United States
GR  - UL1 RR024975-01/RR/NCRR NIH HHS/United States
GR  - F33AR052241/AR/NIAMS NIH HHS/United States
GR  - TL1 RR024978/RR/NCRR NIH HHS/United States
GR  - KL2 RR024977/RR/NCRR NIH HHS/United States
GR  - CA-17229/CA/NCI NIH HHS/United States
GR  - F33 AR052241-01/AR/NIAMS NIH HHS/United States
GR  - AG-02046/AG/NIA NIH HHS/United States
GR  - UL1 RR024975/RR/NCRR NIH HHS/United States
GR  - P30 AR041943/AR/NIAMS NIH HHS/United States
GR  - F33 AR052241/AR/NIAMS NIH HHS/United States
GR  - P30AR041943/AR/NIAMS NIH HHS/United States
GR  - P30 AR041943-100031/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100617
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Culture Media)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 5)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (SFRP1 protein, human)
RN  - 0 (SFRP2 protein, human)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 776B62CQ27 (Decitabine)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Acetylation/drug effects
MH  - Black or African American
MH  - Azacitidine/analogs & derivatives/pharmacology
MH  - Cell Division/physiology
MH  - Cells, Cultured
MH  - Culture Media/pharmacology
MH  - DNA Methylation/*physiology
MH  - Decitabine
MH  - Dermis/cytology/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Epigenesis, Genetic/*physiology
MH  - Fibroblasts/cytology/physiology
MH  - Fibrosis
MH  - Gene Expression Profiling
MH  - Gene Silencing
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - Histones/metabolism
MH  - Humans
MH  - Hydroxamic Acids/pharmacology
MH  - Insulin-Like Growth Factor Binding Protein 5/genetics/metabolism
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Keloid/*genetics/*pathology/physiopathology
MH  - Membrane Proteins/genetics/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Wound Healing/*genetics
PMC - PMC2939920
MID - NIHMS231168
COIS- CONFLICT OF INTEREST The authors state no conflict of interest.
EDAT- 2010/06/18 06:00
MHDA- 2010/10/12 06:00
PMCR- 2010/10/01
CRDT- 2010/06/18 06:00
PHST- 2010/06/18 06:00 [entrez]
PHST- 2010/06/18 06:00 [pubmed]
PHST- 2010/10/12 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - S0022-202X(15)34563-2 [pii]
AID - 10.1038/jid.2010.162 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2010 Oct;130(10):2489-96. doi: 10.1038/jid.2010.162. Epub 2010 
      Jun 17.