PMID- 18385064
OWN - NLM
STAT- MEDLINE
DCOM- 20080624
LR  - 20191023
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 49
IP  - 4
DP  - 2008 Apr
TI  - The effect of TGF-beta2 on elastin, type VI collagen, and components of the 
      proteolytic degradation system in human optic nerve astrocytes.
PG  - 1464-72
LID - 10.1167/iovs.07-1053 [doi]
AB  - PURPOSE: To investigate the effect of transforming growth factor (TGF)-beta2 on 
      the expression of (1) elastin and type VI collagen (ColVI), (2) extracellular 
      matrix (ECM)-degrading matrix-metalloproteinases (MMPs) and regulators of their 
      activity/activation, and (3) the involvement of connective tissue growth factor 
      (CTGF) in the TGF-beta2-mediated regulations in cultured human type-1A and -1B 
      optic nerve astrocytes. METHODS: Astrocytes were isolated from the optic nerves 
      of 11 donors aged 19 to 62 years without a history of eye disease from the 
      prelaminar (type 1B, five explants) or postlaminar (type 1A, six explants) 
      region. Cultures of passages 3 to 5 were treated with 1 ng/mL recombinant human 
      TGF-beta2 for 72 hours, and regulatory effects on the expression of elastin and 
      the ColVI chains alpha1, alpha2, and alpha3; MMP-1, -2, -3, -7, -9, -12, and -13; 
      tissue inhibitors of MMPs (TIMPs) -1, -2, and -3; plasminogen activator inhibitor 
      1 (PAI-1); and urokinase and tissue plasminogen activators (uPA, tPA) were 
      initially analyzed by RT-PCR and confirmed and quantified by real-time PCR 
      (rtPCR). The regulation of proteins was studied by Western blot analysis, and 
      MMP-2 activity was assessed by gelatin zymography. The involvement of CTGF was 
      tested by knockdown experiments with CTGF-small interfering (si)RNA. RESULTS: 
      TGF-beta2 increased the expression of elastin (5X[rtPCR]/6X[WB]), ColVIalpha2 
      (3X/5X), ColVIalpha3 (7X/9X), MMP-2 (2X/2X), TIMP-1/-3 (1.5X/2X), and PAI-1 
      (8X/4X) compared to untreated controls. tPA was reduced to 0.5X. MMP-1, -3, -7, 
      and -12 and TIMP-2 were expressed but were not responsive to TGF-beta2. MMP-9 and 
      -13 and uPA were marginally expressed and close to the detection threshold. MMP-2 
      activity was significantly reduced in gelatin zymography. Transfection of 
      CTGF-siRNA blocked TGF-beta2-mediated activation of elastin and ColVI but had no 
      effect on MMP-2 and PAI-1 induction. Type 1A and 1B astrocytes reacted 
      identically. CONCLUSIONS: TGF-beta2 induces expression of elastin and ColVI and 
      thereby could contribute to the increase of type VI collagen fibers in the tissue 
      septae and the elastotic changes typically observed in POAG. With the concurrent 
      activation of TIMP-1 and -3 and PAI-1 and the repression of tPA, TGF-beta2 could 
      negatively regulate the activity and activation of MMPs. This effect could 
      further amplify ECM accumulation and elastosis.
FAU - Neumann, Carolin
AU  - Neumann C
AD  - Department of Anatomy II, Friedrich Alexander University, Erlangen, Germany.
FAU - Yu, Alice
AU  - Yu A
FAU - Welge-Lussen, Ulrich
AU  - Welge-Lussen U
FAU - Lutjen-Drecoll, Elke
AU  - Lutjen-Drecoll E
FAU - Birke, Marco
AU  - Birke M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (CCN2 protein, human)
RN  - 0 (Collagen Type VI)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Transforming Growth Factor beta2)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - 9007-58-3 (Elastin)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adult
MH  - Astrocytes/*drug effects/metabolism
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Collagen Type VI/*metabolism
MH  - Connective Tissue Growth Factor
MH  - Elastin/*metabolism
MH  - Fluorescent Antibody Technique, Indirect
MH  - Humans
MH  - Immediate-Early Proteins/genetics/metabolism
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Matrix Metalloproteinases/*metabolism
MH  - Microscopy, Fluorescence
MH  - Middle Aged
MH  - Optic Nerve/*cytology
MH  - RNA, Small Interfering/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
MH  - Transforming Growth Factor beta2/*pharmacology
EDAT- 2008/04/04 09:00
MHDA- 2008/06/25 09:00
CRDT- 2008/04/04 09:00
PHST- 2008/04/04 09:00 [pubmed]
PHST- 2008/06/25 09:00 [medline]
PHST- 2008/04/04 09:00 [entrez]
AID - 49/4/1464 [pii]
AID - 10.1167/iovs.07-1053 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1464-72. doi: 10.1167/iovs.07-1053.