scholarly journals Resibufogenin suppresses transforming growth factor‐β‐activated kinase 1‐mediated nuclear factor‐κB activity through protein kinase C‐dependent inhibition of glycogen synthase kinase 3

2018 ◽  
Vol 109 (11) ◽  
pp. 3611-3622 ◽  
Author(s):  
Lu Liu ◽  
Yang Liu ◽  
Xiaojia Liu ◽  
Na Zhang ◽  
Genxiang Mao ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Glycogen Synthase ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Glycogen Synthase Kinase 3 ◽  
Nuclear Factor ◽  
Kinase C ◽  
Dependent Inhibition

Co-activation of synovial fibroblasts by laminin-111 and transforming growth factor-β induces expression of matrix metalloproteinases 3 and 10 independently of nuclear factor-κB

2007 ◽  
Vol 67 (4) ◽  
pp. 559-562 ◽  
Author(s):  
K Warstat ◽  
T Pap ◽  
G Klein ◽  
S Gay ◽  
W K Aicher
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Synovial Fibroblasts ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
The Matrix ◽  
Specific Tissue ◽  
Significant Expression

We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-β induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix proteases (TIMPs). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative reverse transcription–polymerase chain reaction. Production of MMPs was monitored by a multiplexed immunoarray. Signal transduction pathways were studied by immunoblotting. Attachment of synovial fibroblasts to LM-111 in the presence of transforming growth factor-β induced significant increases in MMP-3 mRNA (12.35-fold, p<0.001) and protein (mean 62 ng/ml, sixfold, p<0.008) and in expression of MMP-10 mRNA (11.68-fold, p<0.05) and protein (54 ng/ml, 20-fold, p⩾0.02). All other TIMPs and MMPs investigated failed to show this LM-111-facilitated transforming growth factor-β response. No phosphorylation of nuclear factor-κB was observed. We conclude that co-stimulation of synovial fibroblasts by LM-111 together with transforming growth factor-β suffices to induce significant expression of MMP-3 and MMP-10 by synovial fibroblasts and that this induction is independent of nuclear factor-κB phosphorylation.

scholarly journals α1B-Adrenergic receptor phosphorylation and desensitization induced by transforming growth factor-β

2002 ◽  
Vol 368 (2) ◽  
pp. 581-587 ◽  
Author(s):  
M. Teresa ROMERO-ÁVILA ◽  
C. Fabián FLORES-JASSO ◽  
J. Adolfo GARCÍA-SÁINZ
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Receptor Phosphorylation ◽  
Kinase C ◽  
Phosphoinositide 3 Kinase

Transforming growth factor-β (TGF-β) induced α1B-adrenergic receptor phosphorylation in Rat-1 fibroblasts stably expressing these adrenoceptors. This effect of TGF-β was rapid, reaching a maximum within 30min and decreasing thereafter, and concentration-dependent (EC50 0.3pM). The phosphoinositide 3-kinase inhibitors wortmannin and LY294002, and the protein kinase C inhibitors staurosporine, Ro 318220 and bisindolylmaleimide, blocked the effect of this growth factor. α1B-Adrenergic receptor phosphorylation was associated with desensitization, as indicated by a reduction in the adrenergic-mediated production of [3H]inositol phosphates. Phosphorylation of α1B-adrenergic receptors by TGF-β was also observed in Cos-1 cells transfected with the receptor. Co-transfection of the dominant-negative mutant of the regulatory subunit of phosphoinositide 3-kinase (Δp85) inhibited the phosphorylation of α1B-adrenergic receptors induced by TGF-β. Our results indicate that activation of TGF-β receptors induces α1B-adrenergic receptor phosphorylation and desensitization. The data suggest that phosphoinositide 3-kinase and protein kinase C play key roles in this effect of TGF-β.

l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor κB and down-regulation of transforming growth factor β and connective tissue growth factor

2015 ◽  
Vol 35 (2) ◽  
pp. 135-146 ◽  
Author(s):  
JE Pérez-Vargas ◽  
N Zarco ◽  
P Vergara ◽  
M Shibayama ◽  
J Segovia ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Hepatic Cirrhosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Tissue Growth ◽  
Nuclear Factor

Here we evaluated the ability of l-theanine in preventing experimental hepatic cirrhosis and investigated the roles of nuclear factor-κB (NF-κB) activation as well as transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) regulation. Experimental hepatic cirrhosis was established by the administration of carbon tetrachloride (CCl4) to rats (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same time, adding l-theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum access to water and food throughout the treatment period. CCl4 treatment promoted NF-κB activation and increased the expression of both TGF-β and CTGF. CCl4 increased the serum activities of alanine aminotransferase and γ-glutamyl transpeptidase and the degree of lipid peroxidation, and it also induced a decrease in the glutathione and glutathione disulfide ratio. l-Theanine prevented increased expression of NF-κB and down-regulated the pro-inflammatory (interleukin (IL)-1β and IL-6) and profibrotic (TGF-β and CTGF) cytokines. Furthermore, the levels of messenger RNA encoding these proteins decreased in agreement with the expression levels. l-Theanine promoted the expression of the anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13. Liver hydroxyproline contents and histopathological analysis demonstrated the anti-fibrotic effect of l-theanine. In conclusion, l-theanine prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals.

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