scholarly journals Transforming growth factor β (TGFβ) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts

1987 ◽  
Vol 247 (3) ◽  
pp. 597-604 ◽  
Author(s):  
J Varga ◽  
J Rosenbloom ◽  
S A Jimenez
Keyword(s):  
Steady State ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Fold Increase ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Human Dermal Fibroblasts ◽  
Tgf Beta ◽  
Normal Human ◽  
Normal Human Dermal Fibroblasts

It has been previously shown that transforming growth factor beta (TGF beta) is capable of stimulating fibroblast collagen and fibronectin biosynthesis. The purpose of this study was to examine the mechanisms involved in TGF beta stimulation of fibroblast biosynthetic activity. Our results indicate that TGF beta causes a marked enhancement of the production of types I and III collagens and fibronectin by cultured normal human dermal fibroblasts. The rate of collagen production by fibroblasts exposed to TGF beta was 2-3-fold greater than that of control cells. These effects were associated with a 2-3-fold increase in the steady-state amounts of types I and III collagen mRNAs and a 5-8-fold increase in the amounts of fibronectin mRNAs as determined by dot-blot hybridization with specific cloned cDNA probes. In addition, the increased production of collagen and fibronectin and the increased amounts of their corresponding mRNAs remained elevated for at least 72 h after removal of TGF beta. These findings suggest that TGF beta may play a major role in the normal regulation of extracellular matrix production in vivo and may contribute to the development of pathological states of fibrosis.

scholarly journals Effects of GABA on the expression of type I collagen gene in normal human dermal fibroblasts

2016 ◽  
Vol 81 (2) ◽  
pp. 376-379 ◽  
Author(s):  
Eriko Uehara ◽  
Hideki Hokazono ◽  
Takako Sasaki ◽  
Hidekatsu Yoshioka ◽  
Noritaka Matsuo
Keyword(s):  
Type I Collagen ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Collagen Gene ◽  
Human Dermal Fibroblasts ◽  
Normal Human ◽  
Normal Human Dermal Fibroblasts

scholarly journals Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta.

1987 ◽  
Vol 165 (1) ◽  
pp. 251-256 ◽  
Author(s):  
A E Postlethwaite ◽  
J Keski-Oja ◽  
H L Moses ◽  
A H Kang
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Critical Role ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Tgf Beta ◽  
Chemotactic Migration ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-beta) is a potent chemoattractant in vitro for human dermal fibroblasts. Intact disulfide and perhaps the dimeric structure of TGF-beta is essential for its ability to stimulate chemotactic migration of fibroblasts, since reduction with 2-ME results in a marked loss of its potency as a chemoattractant. Although epidermal growth factor (EGF) appears to be capable of modulating some effects of TGF-beta, it does not alter the chemotactic response of fibroblasts to TGF-beta. Specific polyvalent rabbit antibodies to homogeneously pure TGF-beta block its chemotactic activity but has no effect on the other chemoattractants tested (platelet-derived growth factor, fibronectin, and denatured type I collagen). Since TGF-beta is secreted by a variety of neoplastic and normal cells including platelets, monocytes/macrophages, and lymphocytes, it may play a critical role in vivo in embryogenesis, host response to tumors, and the repair response that follows damage to tissues by immune and nonimmune reactions.

scholarly journals Validation of in vitro assays in three-dimensional human dermal constructs

2018 ◽  
Vol 41 (11) ◽  
pp. 779-788 ◽  
Author(s):  
Ayesha Idrees ◽  
Valeria Chiono ◽  
Gianluca Ciardelli ◽  
Siegfried Shah ◽  
Richard Viebahn ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dermal Fibroblasts ◽  
In Vitro Assays ◽  
Dimensional System ◽  
Type I ◽  
Human Dermal Fibroblasts ◽  
Cell Viability Assay ◽  
Normal Human ◽  
Normal Human Dermal Fibroblasts

Three-dimensional cell culture systems are urgently needed for cytocompatibility testing of biomaterials. This work aimed at the development of three-dimensional in vitro dermal skin models and their optimization for cytocompatibility evaluation. Initially “murine in vitro dermal construct” based on L929 cells was generated, leading to the development of “human in vitro dermal construct” consisting of normal human dermal fibroblasts in rat tail tendon collagen type I. To assess the viability of the cells, different assays CellTiter-Blue®, RealTime-Glo™ MT, and CellTiter-Glo® (Promega) were evaluated to optimize the best-suited assay to the respective cell type and three-dimensional system. Z-stack imaging (Live/Dead and Phalloidin/DAPI-Promokine) was performed to visualize normal human dermal fibroblasts inside matrix revealing filopodia-like morphology and a uniform distribution of normal human dermal fibroblasts in matrix. CellTiter-Glo was found to be the optimal cell viability assay among those analyzed. CellTiter-Blue reagent affected the cell morphology of normal human dermal fibroblasts (unlike L929), suggesting an interference with cell biological activity, resulting in less reliable viability data. On the other hand, RealTime-Glo provided a linear signal only with a very low cell density, which made this assay unsuitable for this system. CellTiter-Glo adapted to three-dimensional dermal construct by optimizing the “shaking time” to enhance the reagent penetration and maximum adenosine triphosphate release, indicating 2.4 times higher viability value by shaking for 60 min than for 5 min. In addition, viability results showed that cells were viable inside the matrix. This model would be further advanced with more layers of skin to make a full thickness model.

scholarly journals Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: importance of hyaluronan for the mitogenic response of PDGF-BB

2007 ◽  
Vol 404 (2) ◽  
pp. 327-336 ◽  
Author(s):  
Lingli Li ◽  
Trias Asteriou ◽  
Berit Bernert ◽  
Carl-Henrik Heldin ◽  
Paraskevi Heldin
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Fold Increase ◽  
Nuclear Factor Κb ◽  
Transforming Growth Factor Β1 ◽  
Dermal Fibroblasts ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Human Dermal Fibroblasts ◽  
High Level

The glycosaminoglycan hyaluronan is important in many tissuerepair processes. We have investigated the synthesis of hyaluronan in a panel of cell lines of fibroblastic and epithelial origin in response to PDGF (platelet-derived growth factor)-BB and other growth factors. Human dermal fibroblasts exhibited the highest hyaluronan-synthesizing activity in response to PDGF-BB. Analysis of HAS (hyaluronan synthase) and HYAL (hyaluronidase) mRNA expression showed that PDGF-BB treatment induced a 3-fold increase in the already high level of HAS2 mRNA, and increases in HAS1 and HYAL1 mRNA, whereas the levels of HAS3 and HYAL2 mRNA were not affected. Furthermore, PDGF-BB also increased the amount and activity of HAS2 protein, but not of HYAL1 and HYAL2 proteins. Using inhibitors for MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 1/2] (U0126) and for PI3K (phosphoinositide 3-kinase) (LY294002), as well as the SN50 inhibitor, which prevents translocation of the active NF-κB (nuclear factor κB) to the nucleus, we observed a complete inhibition of both HAS2 transcriptional activity and hyaluronan synthesis, whereas inhibitors of other signalling pathways were without any significant effect. TGF-β1 (transforming growth factor-β1) did not increase the activity of hyaluronan synthesis in dermal fibroblasts, but increased the activity of HYALs. Importantly, inhibition of hyaluronan binding to its receptor CD44 by the monoclonal antibody Hermes-1, inhibited PDGF-BB-stimulated [3H]thymidine incorporation of dermal fibroblasts. We conclude that the ERK MAPK and PI3K signalling pathways are necessary for the regulation of hyaluronan synthesis by PDGF-BB, and that prevention of its binding to CD44 inhibits PDGF-BB-induced cell growth.

scholarly journals Protective Effects of Indole 3-Acetonitrile-4-Methoxy-2-S-β-d-Glucopyranoside From Nasturtium officinale R. Br. Against Ultraviolet B-Induced Photodamage in Normal Human Dermal Fibroblasts

2019 ◽  
Vol 14 (8) ◽  
pp. 1934578X1987242
Author(s):  
Yumin Kim ◽  
Kyung Suk Bae
Keyword(s):  
Dermal Fibroblasts ◽  
Ultraviolet B ◽  
Type I ◽  
Protective Effects ◽  
Human Dermal Fibroblasts ◽  
Nasturtium Officinale ◽  
Type I Procollagen ◽  
Matrix Metalloproteinase 1 ◽  
Normal Human ◽  
Normal Human Dermal Fibroblasts

Ultraviolet radiation induces skin photoaging, which is associated with the elevation of matrix metalloproteinase-1 (MMP-1) and the decrease of procollagen. Nasturtium officinale plays a well-known role in the treatment of sulfur-containing compounds and their important role in protecting human health. However, their skin protective activity toward UVB-induced photodamage remains unclear. In the present study, we investigated the protective effect of indole 3-acetonitrile-4-methoxy-2- S-β-d-glucopyranoside (IAMG) from N. officinale on UVB-irradiated normal human dermal fibroblasts (NHDF). Our results show that IAMG enhanced NHDF cell migration. The UVB-induced increases in MMP-1 and decrease in type I procollagen were ameliorated by IAMG treatment. Taken together, our data strongly suggest that IAMG from N. officinale could reduce UVB-induced photodamage.

scholarly journals Anti-Aging Effects of Gyrophoric Acid on UVA-Irradiated Normal Human Dermal Fibroblasts

2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2091954
Author(s):  
Joong Hyun Shim
Keyword(s):  
Mrna Expression ◽  
Type I Collagen ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Human Dermal Fibroblasts ◽  
Aging Effects ◽  
Expression Levels ◽  
Normal Human ◽  
Normal Human Dermal Fibroblasts ◽  
Gyrophoric Acid

This research was conducted to identify the anti-aging effects of gyrophoric acid on the skin, using normal human dermal fibroblasts. The anti-aging effects of gyrophoric acid on dermal fibroblasts were demonstrated through cell viability, verification of collagen, type I, alpha 1 (COL1A1)/COL3A1/matrix metalloproteinases 1 (MMP1) messenger ribonucleic acid (mRNA) expression levels with quantitative real-time reverse-transcription polymerase chain reaction, and protein estimation using type I collagen/MMP1-enzyme-linked immunosorbent assay. Further, the effects of gyrophoric acid on superoxide dismutases (SODs)/catalase were investigated by assessing their mRNA expression. In ultraviolet A (UVA)-treated dermal fibroblasts, gyrophoric acid was observed to increase mRNA levels of COL1A1/COL3A1/SOD2 genes and type I collagen protein levels, consistent with its anti-aging role. Furthermore, gyrophoric acid treatment decreased both MMP1 mRNA and protein expression levels. Therefore, the results of this study demonstrate that gyrophoric acid can be considered as an important natural compound with potent anti-aging effects on the skin. Based on the findings of this study, further research about the mechanism of action of gyrophoric acid should be pursued so as to develop novel anti-aging strategies not only in the field of cosmetics but also for healthcare.

scholarly journals Leukoregulin down-regulates type I collagen mRNA levels and promoter activity in human dermal fibroblasts, and counteracts the up-regulation elicited by transforming growth factor-β

1992 ◽  
Vol 284 (3) ◽  
pp. 629-632 ◽  
Author(s):  
A Mauviel ◽  
C H Evans ◽  
J Uitto
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Promoter Activity ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Mrna Levels ◽  
Human Dermal Fibroblasts

Leukoregulin (LR), a T-cell-derived growth factor, modulates fibroblast functions in vitro [Mauviel, Rédini, Hartmann, Loyau & Pujol (1991) J. Cell Biol. 113, 1455-1462]. In the present study, incubation of human dermal fibroblasts with LR (0.1-2 units/ml) resulted in decreases in the mRNA steady-state levels for alpha 1(I), alpha 2(I) and alpha 1(III), but not alpha 2(V), collagen genes. LR also down-regulated alpha 2(I) collagen promoter activity in transient cell transfections of control cells as well as those incubated with transforming growth factor-beta, a potent up-regulator of collagen type I gene expression. Thus LR is a strong inhibitor of type I collagen gene expression, acting at the level of transcription.

scholarly journals Prostaglandin E2 induces Skin Aging via E-prostanoid 1 in Normal Human Dermal Fibroblasts

2019 ◽  
Author(s):  
Joong Hyun Shim
Keyword(s):  
Prostaglandin E2 ◽  
Messenger Rna ◽  
Collagen Type ◽  
Collagen Type I ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Mrna Levels ◽  
Human Dermal Fibroblasts ◽  
Normal Human ◽  
Normal Human Dermal Fibroblasts

Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca2+ concentration in NHDFs. These results indicated that PGE2 is directly associated with EP1 pathway–regulated ERK1/2 and inositol trisphosphate (IP3) signaling in NHDFs.

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