Stress-relaxation and contraction of a collagen matrix induces expression of TGF-β and triggers apoptosis in dermal fibroblasts

2000 ◽  
Vol 78 (4) ◽  
pp. 427-436 ◽  
Author(s):  
M Varedi ◽  
E E Tredget ◽  
A Ghahary ◽  
P G Scott
Keyword(s):  
Mechanical Properties ◽  
Growth Factor ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Collagen Matrix ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Collagen Matrices ◽  
Matrix Metalloproteinase 1 ◽  
Tgf Β1

Extracellular matrix serves as a scaffold for cells and can also regulate gene expression and ultimately cell behaviour. In this study, we compared the effects of three forms of type I collagen matrix, which differed only in their mechanical properties, and plastic on the expression of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-1 (collagenase), and type I collagen and on the growth and survival of human dermal fibroblasts. These effects were correlated with alterations in cell morphology and organization of intracellular actin. Cells in detached or stress-relaxed matrices were spherical, lacked stress fibres, and showed increased TGF-β1 mRNA compared to the cells in anchored collagen matrices or on plastic, which were polygonal or bipolar and formed stress fibres. The levels of TGF-β measured by bioassay were higher in detached and stress-relaxed collagen matrices, than in anchored collagen matrices. Cells on plastic contained little or no immunoreactive TGF-β, while most cells in collagen matrices were stained. The levels of collagenase mRNA were significantly higher in all the collagen matrix cultures compared to those on plastic, but there were no statistically significant differences between them. Levels of mRNA for procollagen type I were not significantly affected by culture in the collagen matrices. Apoptotic fibroblasts were detected by the TUNEL assay in detached (5.7%) and to a lesser extent in stress-relaxed (2.2%) matrices, but none were observed in anchored collagen matrices or on plastic. These results show that alterations in the mechanical properties of matrix can induce the expression of TGF-β and trigger apoptosis in dermal fibroblasts. They further suggest that inability to reorganize this matrix could be responsible for the maintenance of the fibroproliferative phenotype associated with fibroblasts in hypertrophic scarring. Key words: transforming growth factor-β, apoptosis, fibroblasts.

Collagen matrices attenuate the collagen-synthetic response of cultured fibroblasts to TGF-beta

1995 ◽  
Vol 108 (3) ◽  
pp. 1251-1261 ◽  
Author(s):  
R.A. Clark ◽  
L.D. Nielsen ◽  
M.P. Welch ◽  
J.M. McPherson
Keyword(s):  
Growth Factor ◽  
Granulation Tissue ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Collagen Matrix ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Collagen Gels ◽  
Type I Procollagen ◽  
Growth Factor Beta

Transforming growth factor-beta, a potent modulator of cell function, induces fibroblasts cultured on plastic to increase collagen synthesis. In 5- and 7-day porcine skin wounds, which have minimal to moderate collagen matrix, respectively, transforming growth factor-beta and type I procollagen were coordinately expressed throughout the granulation tissue. However, in 10-day collagen-rich granulation tissue type I procollagen expression diminished despite persistence of transforming growth factor-beta. To investigate whether collagen matrix attenuates the collagen-synthetic response of fibroblasts to transforming growth factor-beta, we cultured human dermal fibroblasts in conditions that simulate collagen-rich granulation tissue. Therefore, human dermal fibroblasts were suspended in attached collagen gels and collagen and noncollagen production was assayed in the absence and presence of transforming growth factor-beta. Although transforming growth factor-beta stimulated collagen synthesis by fibroblasts cultured in the collagen gels, these fibroblasts consistently produced less collagen than similarly treated fibroblasts cultured on plastic. This phenomenon was not secondary to nonspecific binding of transforming growth factor-beta to the collagen matrix. Fibroblasts cultured in a fibrin gel responded to transforming growth factor-beta similarly to fibroblasts cultured on plastic. Using immunofluorescence probes to type I procollagen, we observed that transforming growth factor-beta increased type I procollagen expression in most fibroblasts cultured on plastic, but only in occasional fibroblasts cultured in collagen gels. From these data we conclude that collagen matrices attenuate the collagen synthetic response of fibroblast to transforming growth factor-beta in vitro and possibly in vivo.

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 Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

2020 ◽  
Vol 21 (22) ◽  
pp. 8693
Author(s):  
Young Eun Choi ◽  
Min Ji Song ◽  
Mari Hara ◽  
Kyoko Imanaka-Yoshida ◽  
Dong Hun Lee ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Mrna Level ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Cell Physiology ◽  
Type I ◽  
Tenascin C ◽  
Matrix Metalloproteinase 1

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. In this study, we found that the Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of transforming growth factor-β1 (TGF-β1) mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

scholarly journals Decreased MiR-30a promotes TGF-β1-mediated arachnoid fibrosis in post-hemorrhagic hydrocephalus

2020 ◽  
Vol 11 (1) ◽  
pp. 60-74
Author(s):  
Chaohong Zhan ◽  
Gelei Xiao ◽  
Xiangyang Zhang ◽  
Xiaoyu Chen ◽  
Zhiping Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Intraventricular Hemorrhage ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Ventricular System ◽  
Type I ◽  
Cerebral Ventricles ◽  
The Right ◽  
Tgf Β1

AbstractBackgroundFibrosis in the ventricular system is closely associated with post-hemorrhagic hydrocephalus (PHH). It is characterized by an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH). The activation of transforming growth factor-β1 (TGF-β1) may be involved in thrombin-induced arachnoid fibrosis.MethodsA rat model of PHH was established by injection of autologous non-anticoagulated blood from the right femoral artery into the lateral ventricles. Differential expression of miR-30a was detected in rat arachnoid cells by RNA sequencing. AP-1, c-Fos, and TRAF3IP2 were knocked down in primary arachnoid cells, and the degree of arachnoid fibrosis was assessed.ResultsDecreased expression of miR-30a and increased expression of TRAF3IP2, TGF-β1, and α-SMA were detected in the arachnoid cells of PHH rat. Besides, overexpression of miR-30a targets TRAF3IP2 mRNA 3′UTR and inhibits the expression of TRAF3IP2, TGF-β1, and α-SMA in the primary arachnoid cells. Furthermore, TRAF3IP2 activates AP-1 to promote arachnoid fibrosis. The content of type I collagen in the primary arachnoid cells was reduced after the silencing of AP-1 and TRAF3IP2.ConclusionsThis study identified a miR-30a-regulated mechanism of arachnoid fibrosis, suggesting a previously unrecognized contribution of miR-30a to the pathogenesis of fibrosis in the ventricular system. These results might provide a new target for the clinical diagnosis and treatment of PHH.

scholarly journals Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

2020 ◽  
Author(s):  
Young Eun Choi ◽  
Min Ji Song ◽  
Mari Hara ◽  
Kyoko Imanaka-Yoshida ◽  
Dong Hun Lee ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Mrna Level ◽  
Collagen Matrix ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Cell Physiology ◽  
Type I ◽  
Tenascin C ◽  
Matrix Metalloproteinase 1

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

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