scholarly journals Interleukin-1β prevents the stimulatory effect of transforming growth factor-β on collagen gene expression in human skin fibroblasts

1990 ◽  
Vol 271 (3) ◽  
pp. 827-830 ◽  
Author(s):  
J Heino ◽  
T Heinonen
Keyword(s):  
Gene Expression ◽  
Human Skin ◽  
Skin Fibroblasts ◽  
Collagen Gene ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Human Skin Fibroblasts ◽  
Collagen Mrna ◽  
Collagen Gene Expression ◽  
Beta 2

Transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2) are well-characterized strong inducers of collagen gene expression. A 100 pM concentration of TGF-beta 1 or TGF-beta 2 increases pro alpha 1(I) collagen mRNA levels in human skin fibroblasts 6.6-fold and 7.0-fold respectively, and also increases the accumulation of procollagens in the cell culture medium. Interleukin-1 beta (IL-1 beta) is an inflammatory mediator which also regulates connective tissue metabolism. A small concentration of IL-1 beta (0.01-1.0 unit/ml) slightly increases pro alpha 1(I) collagen mRNA levels (2.2-fold). Here we provide evidence that IL-1 beta prevents the stimulatory effect of TGFs-beta on collagen synthesis in human skin fibroblasts. An IL-1 beta concentration of 1 unit/ml is enough to keep pro alpha 1(I) collagen mRNA levels at control values in cells stimulated by 100 pM-TGF-beta 1. Thus the results indicate that IL-1 beta inhibits collagen synthesis in cells activated by TGFs-beta, whereas it does not significantly change or might even stimulate collagen gene expression in non-activated cells.

scholarly journals The protein phosphatase inhibitor okadaic acid suppresses type I collagen gene expression in cultured fibroblasts at the transcriptional level

1995 ◽  
Vol 308 (3) ◽  
pp. 995-999 ◽  
Author(s):  
J Westermarck ◽  
E Ilvonen ◽  
V M Kähäri
Keyword(s):  
Gene Expression ◽  
Type I Collagen ◽  
Protein Phosphatases ◽  
Type I ◽  
Collagen Gene ◽  
Mrna Levels ◽  
Collagen Mrna ◽  
Collagen Gene Expression ◽  
Nih 3T3 ◽  
Collagen Promoter

Type I collagen is the most abundant component of the extracellular matrix of human connective tissues. We have examined the effect of okadaic acid (OA), an inhibitor of phosphoserine- and-phosphothreonine-specific protein phosphatases 1 and 2A, on type I collagen gene expression by fibroblasts in culture. Treatment of human skin fibroblasts with OA potently reduced type I and type III collagen mRNA levels, maximally by over 90%. The inhibitory effect of OA on type I and III collagen mRNA abundance was not prevented by cycloheximide, and was not affected by simultaneous treatment with dexamethasone or retinoic acid. OA also abrogated the enhancing effect of transforming growth factor-beta (TGF-beta) on type I and III collagen mRNA levels. Treatment of transiently transfected NIH-3T3 fibroblasts with OA suppressed the activity of a 3.5 kb human pro alpha 2(I) collagen promoter/chloramphenicol acetyltransferase construct maximally, by 70%. In addition, OA treatment of NIH-3T3 cells abrogated enhancement of pro alpha 2(I) collagen promoter activity by TGF-beta. These results indicate that protein phosphatases 1 and 2A have an important role as positive regulators of type I and III collagen gene expression. The results also suggest that selective inhibition of activity of protein phosphatases 1 and 2A may offer a novel approach for preventing excessive collagen accumulation in fibrotic disorders.

scholarly journals Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

1993 ◽  
Vol 4 (6) ◽  
pp. 637-645 ◽  
Author(s):  
A Igarashi ◽  
H Okochi ◽  
D M Bradham ◽  
G R Grotendorst
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Connective Tissue ◽  
Human Skin ◽  
Connective Tissue Growth Factor ◽  
Wound Repair ◽  
Tissue Growth ◽  
Skin Fibroblasts ◽  
Tgf Beta ◽  
Human Skin Fibroblasts

Connective tissue growth factor (CTGF) is a cysteine-rich peptide that exhibits platelet-derived growth factor (PDGF)-like biological and immunological activities. CTGF is a member of a family of peptides that include serum-induced immediate early gene products, a v-src-induced peptide, and a putative avian transforming gene, nov. In the present study, we demonstrate that human foreskin fibroblasts produce high levels of CTGF mRNA and protein after activation with transforming growth factor beta (TGF-beta) but not other growth factors including PDGF, epidermal growth factor, and basic fibroblast growth factor. Because of the high level selective induction of CTGF by TGF-beta, it appears that CTGF is a major autocrine growth factor produced by TGF-beta-treated human skin fibroblasts. Cycloheximide did not block the large TGF-beta stimulation of CTGF gene expression, indicating that it is directly regulated by TGF-beta. Similar regulatory mechanisms appear to function in vivo during wound repair where there is a coordinate expression of TGF-beta 1 before CTGF in regenerating tissue, suggesting a cascade process for control of tissue regeneration and repair.

TGF-beta and collagen-alpha 1 (I) gene expression are increased in hepatic acinar zone 1 of rats with iron overload

1994 ◽  
Vol 267 (5) ◽  
pp. G908-G913 ◽  
Author(s):  
K. Houglum ◽  
P. Bedossa ◽  
M. Chojkier
Keyword(s):  
Gene Expression ◽  
Lipid Peroxidation ◽  
Iron Overload ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Collagen Gene ◽  
Tgf Beta ◽  
Collagen Gene Expression ◽  
I Gene

We have shown that lipid peroxidation stimulates collagen-alpha 1 (I) gene transcription in cultured cells. Because iron is a transitional metal known to induce lipid peroxidation, we investigated whether hepatic lipid peroxidation modulates collagen gene expression in iron-overloaded rats. In this animal model of hemochromatosis, we show colocalization with iron in the hepatic acinar zone 1 of both lipid peroxidation and increased collagen-alpha 1 (I) transcripts, using immunohistochemistry for malondialdehyde-protein adducts and in situ hybridization, respectively. Iron overload stimulated the expression of the cytokine transforming growth factor-beta (TGF-beta) in acinar zone 1, in spite of the minor degree of hepatocellular necrosis and inflammation. The formation of reactive aldehydes and TGF-beta, both inducers of collagen gene expression, may play a role in the stimulation of hepatic collagen production in iron overload. These mechanisms could be a link between iron overload and fibrosis in genetic hemochromatosis.

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