PMID- 25865370
OWN - NLM
STAT- MEDLINE
DCOM- 20160517
LR  - 20150729
IS  - 1600-0625 (Electronic)
IS  - 0906-6705 (Linking)
VI  - 24
IP  - 8
DP  - 2015 Aug
TI  - Decorin-expressing adenovirus decreases collagen synthesis and upregulates MMP 
      expression in keloid fibroblasts and keloid spheroids.
PG  - 591-7
LID - 10.1111/exd.12719 [doi]
AB  - Decorin is a natural transforming growth factor-beta1 (TGF-beta1) antagonist. Reduced 
      decorin synthesis is associated with dermal scarring, and increased decorin 
      expression appears to reduce scar tissue formation. To investigate the 
      therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and 
      keloid-derived fibroblasts (KFs) were transduced with decorin-expressing 
      adenovirus (dE1-RGD/GFP/DCN), and we examined the therapeutic potential of 
      decorin-expressing Ad for treating pathologic skin fibrosis. Decorin expression 
      was examined by immunofluorescence assay on keloid tissues. HDFs and KFs were 
      transduced with dE1-RGD/GFP/DCN or control virus, and protein levels of decorin, 
      epidermal growth factor receptor (EGFR) and secreted TGF-beta1 were assessed by 
      Western blotting and ELISA. And type I and III collagen, and matrix 
      metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) mRNA levels 
      were measured by real-time RT-PCR. Additionally, we immunohistochemically 
      investigated the expression levels of the major extracellular matrix (ECM) 
      proteins in keloid spheroids transduced with dE1-RGD/GFP/DCN. Lower decorin 
      expression was observed in the keloid region compared to adjacent normal tissues. 
      After treatment with dE1-RGD/GFP/DCN, secreted TGF-beta1 and EGFR protein 
      expressions were decreased in TGF-beta1-treated HDFs and KFs. Also, type I and III 
      collagen mRNA levels were decreased, and the expression of MMP-1 and MMP-3 mRNA 
      was strongly upregulated. In addition, the expression of type I and III collagen, 
      fibronectin and elastin was significantly reduced in dE1-RGD/GFP/DCN-transduced 
      keloid spheroids. These results support the utility of decorin-expressing 
      adenovirus to reduce collagen synthesis in KFs and keloid spheroid, which may be 
      highly beneficial in treating keloids.
CI  - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Lee, Won Jai
AU  - Lee WJ
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Institute 
      for Human Tissue Restoration, Yonsei University, Seoul, Korea.
FAU - Ahn, Hyo Min
AU  - Ahn HM
AD  - Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 
      Korea.
FAU - Roh, Hyun
AU  - Roh H
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Institute 
      for Human Tissue Restoration, Yonsei University, Seoul, Korea.
FAU - Na, Youjin
AU  - Na Y
AD  - Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 
      Korea.
FAU - Choi, Il-Kyu
AU  - Choi IK
AD  - Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 
      Korea.
FAU - Lee, Ju Hee
AU  - Lee JH
AD  - Department of Dermatology and Cutaneous Biology Research Institute, College of 
      Medicine, Yonsei University, Seoul, Korea.
FAU - Kim, Yong Oock
AU  - Kim YO
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Institute 
      for Human Tissue Restoration, Yonsei University, Seoul, Korea.
FAU - Lew, Dae Hyun
AU  - Lew DH
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Institute 
      for Human Tissue Restoration, Yonsei University, Seoul, Korea.
FAU - Yun, Chae-Ok
AU  - Yun CO
AD  - Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 
      Korea.
LA  - eng
GR  - R01 R0CA177932/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150508
PL  - Denmark
TA  - Exp Dermatol
JT  - Experimental dermatology
JID - 9301549
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type III)
RN  - 0 (DCN protein, human)
RN  - 0 (Decorin)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.7 (MMP1 protein, human)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Cells, Cultured
MH  - Collagen Type I/biosynthesis/genetics
MH  - Collagen Type III/biosynthesis/genetics
MH  - Decorin/genetics/*therapeutic use
MH  - Extracellular Matrix Proteins/*biosynthesis/genetics
MH  - Fibroblasts/*metabolism/pathology
MH  - *Gene Expression Regulation
MH  - *Genetic Therapy
MH  - Genetic Vectors/genetics/*pharmacology
MH  - Humans
MH  - Keloid/metabolism/*pathology
MH  - Matrix Metalloproteinase 1/*biosynthesis/genetics
MH  - Matrix Metalloproteinase 3/*biosynthesis/genetics
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Skin/pathology
MH  - Spheroids, Cellular
OTO - NOTNLM
OT  - MMP
OT  - collagen
OT  - decorin-expressing adenovirus
OT  - gene therapy
OT  - keloid
OT  - keloid spheroid
EDAT- 2015/04/14 06:00
MHDA- 2016/05/18 06:00
CRDT- 2015/04/14 06:00
PHST- 2015/04/08 00:00 [accepted]
PHST- 2015/04/14 06:00 [entrez]
PHST- 2015/04/14 06:00 [pubmed]
PHST- 2016/05/18 06:00 [medline]
AID - 10.1111/exd.12719 [doi]
PST - ppublish
SO  - Exp Dermatol. 2015 Aug;24(8):591-7. doi: 10.1111/exd.12719. Epub 2015 May 8.