PMID- 1649834
OWN - NLM
STAT- MEDLINE
DCOM- 19910823
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 266
IP  - 21
DP  - 1991 Jul 25
TI  - Transcriptional and post-transcriptional regulation of 72-kDa gelatinase/type IV 
      collagenase by transforming growth factor-beta 1 in human fibroblasts. 
      Comparisons with collagenase and tissue inhibitor of matrix metalloproteinase 
      gene expression.
PG  - 14064-71
AB  - The temporal aspects and mechanisms of the regulation of the matrix 
      metalloproteinase (MMP) 72-kDa gelatinase/type IV collagenase (MMP-2) by 
      transforming growth factor-beta 1 (TGF-beta 1) were investigated in early passage 
      human gingival fibroblasts and compared with the regulation of the genes for 
      collagenase (MMP-1) and TIMP, the tissue inhibitor of MMPs. Northern 
      hybridization analyses revealed that 1.0 ng/ml TGF-beta 1 increased the abundance 
      of MMP-2 mRNA/cell approximately 1.5-fold at 24 h, an increase similar to that 
      observed in the level of [35S]methionine pulse-labeled MMP-2 at 24 h (1.9-fold). 
      At 48 and 72 h, the increase in MMP-2 mRNA abundance remained elevated by 
      1.5-2.2-fold on a per cell basis whereas TIMP mRNA levels were elevated by up to 
      3.3-fold. In contrast, the relative levels of collagenase mRNA were reduced by 
      66-75%. The changes in the MMP-2, collagenase, and TIMP mRNA concentrations in 
      response to TGF-beta 1 were blocked by cycloheximide indicating that protein 
      synthesis was required to mediate the effects of TGF-beta 1 on these mRNA levels. 
      TGF-beta 1 was also found to increase the half-life of the MMP-2 mRNA from 
      approximately 46 to approximately 150 h but did not alter the stability of TIMP 
      mRNA (t1/2 approximately 60 h). Nuclear run-off transcription assays revealed 
      that MMP-2 gene transcription was increased approximately 5-fold 7 h following 
      TGF-beta 1-treatment but returned to control levels by 24 h. In comparison, 
      increased TIMP gene transcription was only detectable after 24 h whereas 
      collagenase gene transcription, although low in control cells, was undetectable 
      at 24 h. Gene transcription, mRNA levels, and message stability of the genes for 
      the extracellular matrix proteins type I collagen and fibronectin were also 
      increased by TGF-beta 1. Thus, the similarity in the control of MMP-2, alpha 1 
      (I) procollagen, and fibronectin expression at the transcriptional and 
      post-transcriptional levels indicates that these genes may share regulatory 
      elements. In comparison, TGF-beta 1 reduced the level of collagenase mRNA and 
      increased the level of TIMP mRNA as a result of altered transcriptional 
      activities, through pathways that required protein synthesis, and without changes 
      in mRNA stability.
FAU - Overall, C M
AU  - Overall CM
AD  - Medical Research Council Group in Periodontal Physiology, Faculty of Dentistry, 
      University of Toronto, Ontario, Canada.
FAU - Wrana, J L
AU  - Wrana JL
FAU - Sodek, J
AU  - Sodek J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Transforming Growth Factor beta)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.3 (Microbial Collagenase)
SB  - IM
MH  - Blotting, Northern
MH  - Cell Line
MH  - Cell Nucleus/physiology
MH  - Cycloheximide/pharmacology
MH  - Extracellular Matrix Proteins/metabolism
MH  - Gene Expression Regulation
MH  - Glycoproteins/genetics
MH  - Humans
MH  - In Vitro Techniques
MH  - Matrix Metalloproteinase 2
MH  - Metalloendopeptidases/*genetics
MH  - Microbial Collagenase/genetics
MH  - RNA, Messenger/genetics
MH  - Tissue Inhibitor of Metalloproteinases
MH  - Transcription, Genetic
MH  - Transforming Growth Factor beta/*physiology
EDAT- 1991/07/25 00:00
MHDA- 1991/07/25 00:01
CRDT- 1991/07/25 00:00
PHST- 1991/07/25 00:00 [pubmed]
PHST- 1991/07/25 00:01 [medline]
PHST- 1991/07/25 00:00 [entrez]
AID - S0021-9258(18)92810-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1991 Jul 25;266(21):14064-71.