scholarly journals Sequence-specific 1H-NMR assignments and identification of two small antiparallel beta-sheets in the solution structure of recombinant human transforming growth factor alpha.

1989 ◽  
Vol 86 (5) ◽  
pp. 1519-1523 ◽  
Author(s):  
G. T. Montelione ◽  
M. E. Winkler ◽  
L. E. Burton ◽  
E. Rinderknecht ◽  
M. B. Sporn ◽  
...  
Keyword(s):  
Growth Factor ◽  
1H Nmr ◽  
Solution Structure ◽  
Transforming Growth Factor ◽  
Nmr Assignments ◽  
Beta Sheets ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha

scholarly journals The solution structure of human transforming growth factor alpha

1991 ◽  
Vol 198 (3) ◽  
pp. 555-562 ◽  
Author(s):  
Timothy S. HARVEY ◽  
Anthony J. WILKINSON ◽  
Michael J. TAPPIN ◽  
Robert M. COOKE ◽  
Iain D. CAMPBELL
Keyword(s):  
Growth Factor ◽  
Solution Structure ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha

Solution structures of human transforming growth factor .alpha. derived from 1H NMR data

Biochemistry ◽  
1990 ◽  
Vol 29 (34) ◽  
pp. 7805-7813 ◽  
Author(s):  
Tammy Page Kline ◽  
Frank K. Brown ◽  
Stephen C. Brown ◽  
Peter W. Jeffs ◽  
Kenneth D. Kopple ◽  
...  
Keyword(s):  
Growth Factor ◽  
1H Nmr ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Solution Structures ◽  
Nmr Data ◽  
Factor Alpha

scholarly journals Solution structure and dynamics of epidermal growth factor and transforming growth factor alpha.

1992 ◽  
Vol 267 (1) ◽  
pp. 319-322 ◽  
Author(s):  
S J Prestrelski ◽  
T Arakawa ◽  
C S Wu ◽  
K D O'Neal ◽  
K R Westcott ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Solution Structure ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Structure And Dynamics ◽  
Epidermal Growth ◽  
Factor Alpha

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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