PMID- 18172013
OWN - NLM
STAT- MEDLINE
DCOM- 20080501
LR  - 20191224
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 28
IP  - 7
DP  - 2008 Apr
TI  - Novel transcription-factor-like function of human matrix metalloproteinase 3 
      regulating the CTGF/CCN2 gene.
PG  - 2391-413
LID - 10.1128/MCB.01288-07 [doi]
AB  - Matrix metalloproteinase 3 (MMP3) is well known as a secretory endopeptidase that 
      degrades extracellular matrices. Recent reports indicated the presence of MMPs in 
      the nucleus (A. J. Kwon et al., FASEB J. 18:690-692, 2004); however, its function 
      has not been well investigated. Here, we report a novel function of human nuclear 
      MMP3 as a trans regulator of connective tissue growth factor (CCN2/CTGF). 
      Initially, we cloned MMP3 cDNA as a DNA-binding factor for the CCN2/CTGF gene. An 
      interaction between MMP3 and transcription enhancer dominant in chondrocytes 
      (TRENDIC) in the CCN2/CTGF promoter was confirmed by a gel shift assay and 
      chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by 
      overexpressed MMP3, whereas a TRENDIC mutant promoter lost the response. Also, 
      the knocking down of MMP3 suppressed CCN2/CTGF expression. By cytochemical and 
      histochemical analyses, MMP3 was detected in the nuclei of chondrocytic cells in 
      culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. 
      The nuclear translocation of externally added recombinant MMP3 and six putative 
      nuclear localization signals in MMP3 also were shown. Furthermore, we determined 
      that heterochromatin protein gamma coordinately regulates CCN2/CTGF by 
      interacting with MMP3. The involvement of this novel role of MMP3 in the 
      development, tissue remodeling, and pathology of arthritic diseases through 
      CCN2/CTGF regulation thus is suggested.
FAU - Eguchi, Takanori
AU  - Eguchi T
AD  - Department of Biochemistry and Molecular Dentistry, Okayama University Graduate 
      School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, 
      Okayama City, Okayama, Japan. takigawa@md.okayama-u.ac.jp
FAU - Kubota, Satoshi
AU  - Kubota S
FAU - Kawata, Kazumi
AU  - Kawata K
FAU - Mukudai, Yoshiki
AU  - Mukudai Y
FAU - Uehara, Junji
AU  - Uehara J
FAU - Ohgawara, Toshihiro
AU  - Ohgawara T
FAU - Ibaragi, Soichiro
AU  - Ibaragi S
FAU - Sasaki, Akira
AU  - Sasaki A
FAU - Kuboki, Takuo
AU  - Kuboki T
FAU - Takigawa, Masaharu
AU  - Takigawa M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080102
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (CCN2 protein, human)
RN  - 0 (CCN2 protein, mouse)
RN  - 0 (CCN2 protein, rat)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cell Line, Tumor/metabolism
MH  - Cell Nucleus/metabolism
MH  - Chondrocytes/*metabolism
MH  - Connective Tissue Growth Factor
MH  - Consensus Sequence
MH  - Enhancer Elements, Genetic/*genetics
MH  - Female
MH  - Gene Expression Regulation/*genetics
MH  - Humans
MH  - Immediate-Early Proteins/biosynthesis/*genetics
MH  - Intercellular Signaling Peptides and Proteins/biosynthesis/*genetics
MH  - Matrix Metalloproteinase 3/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Osteoarthritis/metabolism
MH  - Protease Inhibitors/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Fusion Proteins/physiology
MH  - Sequence Alignment
MH  - Sequence Homology, Nucleic Acid
PMC - PMC2268440
EDAT- 2008/01/04 09:00
MHDA- 2008/05/02 09:00
PMCR- 2008/08/01
CRDT- 2008/01/04 09:00
PHST- 2008/01/04 09:00 [pubmed]
PHST- 2008/05/02 09:00 [medline]
PHST- 2008/01/04 09:00 [entrez]
PHST- 2008/08/01 00:00 [pmc-release]
AID - MCB.01288-07 [pii]
AID - 1288-07 [pii]
AID - 10.1128/MCB.01288-07 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2008 Apr;28(7):2391-413. doi: 10.1128/MCB.01288-07. Epub 2008 Jan 
      2.