scholarly journals A novel transforming growth factor β2 antisense transcript in mammalian lung

1998 ◽  
Vol 332 (2) ◽  
pp. 297-301 ◽  
Author(s):  
Robina K. COKER ◽  
Geoffrey J. LAURENT ◽  
Karim DABBAGH ◽  
James DAWSON ◽  
Robin J. McANULTY
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Northern Blot Analysis ◽  
Antisense Transcript ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Transforming Growth Factor Β2 ◽  
Mammalian Lung ◽  
Sense Probe

Transforming growth factor (TGF) β2 gene expression was examined in murine, rat and human lung by in situ hybridization with riboprobes. Hybridization signal was observed in a variety of cells with the sense probe, and Northern-blot analysis with this probe demonstrated the presence of a novel 3.5 kb transcript. This first report suggesting the existance of a natural TGFβ2 antisense transcript raises the possibility that such a transcript may play a role in regulating TGFβ2 production.

Transforming growth factor-β2-mediated regulation of C3 gene expression in monocytes

1996 ◽  
Vol 33 (13) ◽  
pp. 1025-1034 ◽  
Author(s):  
Scott M. Drouin ◽  
Joseph A. Carlino ◽  
Scott R. Barnum
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β2 ◽  
C3 Gene

scholarly journals Localisation of transforming growth factor β1 and β3 mRNA transcripts in normal and fibrotic human lung

Thorax ◽  
2001 ◽  
Vol 56 (7) ◽  
pp. 549-556
Author(s):  
R K Coker ◽  
G J Laurent ◽  
P K Jeffery ◽  
R M du Bois ◽  
C M Black ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Lung Tissue ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
In Situ Hybridisation ◽  
Normal Lung ◽  
Gene And Protein Expression ◽  
Mrna Transcripts

BACKGROUNDTransforming growth factor β1 is implicated in the pathogenesis of lung fibrosis. It promotes extracellular matrix accumulation by increasing procollagen synthesis and reducing degradation. TGFβ1 gene and protein expression increase in experimental lung fibrosis, and TGFβ1 antibodies attenuate fibrosis in mice. The role of other TGFβ isoforms is unclear. This study aimed to localise TGFβ1 and TGFβ3 gene expression in fibrotic human lung and compare it with that in normal human lung.METHODSLung tissue from patients with cryptogenic fibrosing alveolitis and fibrosis associated with systemic sclerosis was examined by in situ hybridisation. Macroscopically normal lung from carcinoma resections was used as control tissue. Digoxigenin labelled riboprobes were synthesised from TGFβ isoform specific cDNA templates.RESULTSThe digoxigenin labelled riboprobes were sensitive and permitted precise cellular localisation of mRNA transcripts. TGFβ1 and TGFβ3 mRNA transcripts were widespread in normal lung and localised to alveolar macrophages and bronchiolar epithelium. TGFβ1 but not TGFβ3 mRNA was detected in mesenchymal and endothelial cells. In fibrotic lung tissue mRNA transcripts for both isoforms were also detected in metaplastic type II cells. TGFβ1 gene expression was enhanced in some patients. TGFβ3 was expressed in fibrotic lung but was not consistently altered compared with controls.CONCLUSIONTGFβ1mRNA transcripts were localised in normal and fibrotic human lung and TGFβ3 gene expression in human lung fibrosis was shown for the first time. The results suggest that TGFβ1 may play the predominant role in pathogenesis. It is suggested that TGFβ1 should be the primary target of anticytokine treatments for pulmonary fibrosis.

MOLECULAR CONTROL OF ARTICULAR CARTILAGE DEGENERATION BY TRANSFORMING GROWTH FACTOR ALPHA

2008 ◽  
Vol 31 (4) ◽  
pp. 2
Author(s):  
Tom Appleton ◽  
Shirine Usmani ◽  
John Mort ◽  
Frank Beier
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Growth Factor ◽  
P38 Mapk ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Signalling Pathways ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha ◽  
Articular Cartilage Degeneration

Background: Articular cartilage degeneration is a hallmark of osteoarthritis (OA). We previously identified increased expression of transforming growth factor alpha (TGF?) and chemokine (C-C motif) ligand 2 (CCL2) in articular cartilage from a rat modelof OA (1,2). We subsequently reported that TGF? signalling modified chondrocyte cytoskeletal organization, increased catabolic and decreased anabolic gene expression and suppressed Sox9. Due to other roles in chondrocytes, we hypothesized that the effects ofTGF? on chondrocytes are mediated by Rho/ROCK and MEK/ERK signaling pathways. Methods: Primary cultures of chondrocytes and articularosteochondral explants were treated with pharmacological inhibitors of MEK1/2(U0126), ROCK (Y27632), Rho (C3), p38 MAPK (SB202190) and PI3K (LY294002) to elucidate pathway involvement. Results: Using G-LISA we determined that stimulation of primary chondrocytes with TGF? activates RhoA. Reciprocally, inhibition of RhoA/ROCK but not other signalling pathways prevents modification of the actin cytoskeleton in responseto TGF?. Inhibition of MEK/ERKsignaling rescued suppression of anabolic gene expression by TGF? including SOX9 mRNA and protein levels. Inhibition of MEK/ERK, Rho/ROCK, p38 MAPK and PI3K signalling pathways differentially controlled the induction of MMP13 and TNF? gene expression. TGF? also induced expression of CCL2 specifically through MEK/ERK activation. In turn, CCL2 treatment induced the expression of MMP3 and TNF?. Finally, we assessed cartilage degradation by immunohistochemical detection of type II collagen cleavage fragments generated by MMPs. Blockade of RhoA/ROCK and MEK/ERK signalling pathways reduced the generation of type IIcollagen cleavage fragments in response to TGF? stimulation. Conclusions: Rho/ROCK signalling mediates TGF?-induced changes inchondrocyte morphology, while MEK/ERK signalling mediates the suppression ofSox9 and its target genes, and CCL2 expression. CCL2, in turn, induces the expression of MMP3 and TNF?, two potent catabolic factors known to be involved in OA. These pathways may represent strategic targets for interventional approaches to treating cartilage degeneration in osteoarthritis. References: 1. Appleton CTG et al. Arthritis Rheum 2007;56:1854-68. 2. Appleton CTG et al. Arthritis Rheum 2007; 56:3693-705.

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