The Role of c-Jun N-terminal Kinases 1/2 in Transforming Growth Factor β1-induced Expression of Connective Tissue Growth Factor and Scar Formation in the Cornea

2009 ◽  
Vol 37 (3) ◽  
pp. 727-736 ◽  
Author(s):  
Y Chang ◽  
X-Y Wu
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Transforming Growth Factor ◽  
Corneal Stroma ◽  
Transforming Growth Factor Β ◽  
Tissue Growth ◽  
Scar Formation ◽  
Mrna Levels ◽  
Corneal Scar

Transforming growth factor β1 (TGF-β1) plays an important role in corneal scar formation, mediated by connective tissue growth factor (CTGF). This study was designed to investigate the effect of c-Jun N-terminal kinase (JNK) 1 and 2 on TGF-β1-regulated CTGF gene expression and corneal scar formation in telomerase-immortalized human corneal stroma fibroblast (THSF) cells. The effects of CTGF, TGF-β1 and a JNK inhibitor (SP600125) on the proliferation of THSF cells were studied using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Both CTGF and TGF-β1 increased THSF cell proliferation and SP600125 inhibited this effect. Immunofluorescence analysis showed that TGF-β1 stimulated the activation of JNK1/2 and induced cell migration, effects that were inhibited by SP600125. Analysis by real-time reverse transcription–polymerase chain reaction showed that the mRNA levels of the genes for CTGF, fibronectin and collagen Iα1 in wound and corneal scar formation were reduced by SP600125 pre-treatment.

Transcriptional regulation of connective tissue growth factor by cortisol in osteoblasts

2000 ◽  
Vol 279 (3) ◽  
pp. E570-E576 ◽  
Author(s):  
Renata C. Pereira ◽  
Deena Durant ◽  
Ernesto Canalis
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Growth ◽  
Bone Morphogenetic Protein 2 ◽  
Mrna Levels ◽  
Fetal Rat ◽  
And Function

Glucocorticoids have important effects on osteoblastic function. Connective tissue growth factor (CTGF)/insulin-like growth factor binding protein-related protein 2 (IGFBP-rP2) plays a role in cell adhesion and function. We examined the regulation of CTGF/IGFBP-rP2 synthesis in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). Cortisol caused a time- and dose-dependent increase in CTGF/IGFBP-rP2 mRNA levels in Ob cells. Cycloheximide did not preclude the effect, indicating that it was not protein synthesis dependent. Cortisol increased the rate of CTGF/IGFBP-rP2 transcription and, in transcriptionally arrested Ob cells, did not modify the decay of the transcript. Parathyroid hormone decreased, whereas transforming growth factor-β and, to a lesser extent, bone morphogenetic protein 2 increased CTGF/IGFBP-rP2 mRNA levels, but other hormones and growth factors had no effect. In conclusion, cortisol stimulates CTGF/IGFBP-rP2 transcription in Ob cells. Because CTGF/IGFBP-rP2 binds IGFs, its increased expression could be relevant to the actions of cortisol in bone.

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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