Effect of transforming growth factors‐β on collagen type VI expression in human dermal fibroblasts

Heckmann, Marc; Aumailley, Monique; Chu, Mon‐Li; Timpl, Rupert; Krieg, Thomas

doi:10.1016/0014-5793(92)81151-b

Cited by 37 publications

(23 citation statements)

References 24 publications

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“…Interestingly, when a 2.5-kilobase pair COL6A2 promoter fragment (24) was tested in an identical experimental system, we observed that it did not confer either TGF-␤ or Smad3 responsiveness (not shown), suggesting a differential regulation of the three genes encoding type VI collagen by TGF-␤, where both COL6A1 and COL6A3 are coordinately regulated and are direct Smad targets, whereas COL6A2 is not. These data differ slightly from previous observations indicating specific up-regulation of COL6A3 but not COL6A1 or COL6A2 by TGF-␤, when mRNA steady-state levels were detected after 48 h of stimulation (46). mRNA steady-state levels of COL1A1, which encodes the ␣(1) chain of type I collagen, have been shown previously to be elevated by TGF-␤ (47).…”

Section: Dominant-negative Smad3 and Inhibitory Smad7 Expression Bloccontrasting

confidence: 99%

Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach

Verrecchia

Chu

Mauviel

2001

Journal of Biological Chemistry

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611

472

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Despite major advances in the understanding of the intimate mechanisms of transforming growth factor-␤ (TGF-␤) signaling through the Smad pathway, little progress has been made in the identification of direct target genes. In this report, using cDNA microarrays, we have focussed our attention on the characterization of extracellular matrix-related genes rapidly induced by TGF-␤ in human dermal fibroblasts and attempted to identify the ones whose up-regulation by TGF-␤ is Smad-mediated. For a gene to qualify as a direct Smad target, we postulated that it had to meet the following criteria: (1) rapid (30 min) and significant (at least 2-fold) elevation of steady-state mRNA levels upon TGF-␤ stimulation, (2) activation of the promoter by both exogenous TGF-␤ and co-transfected Smad3 expression vector, (3) up-regulation of promoter activity by TGF-␤ blocked by both dominant-negative Smad3 and inhibitory Smad7 expression vectors, and (4) promoter transactivation by TGF-␤ not possible in Smad3؊/؊ mouse embryo fibroblasts. Using this stringent approach, we have identified COL1A2, COL3A1, COL6A1, COL6A3, and tissue inhibitor of metalloproteases-1 as definite TGF-␤/Smad3 targets. Extrapolation of this approach to other extracellular matrix-related gene promoters also identified COL1A1 and COL5A2, but not COL6A2, as novel Smad targets. Together, these results represent a significant step toward the identification of novel, early-induced Smaddependent TGF-␤ target genes in fibroblasts.

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Section: Dominant-negative Smad3 and Inhibitory Smad7 Expression Bloccontrasting

confidence: 99%

Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach

Verrecchia

Chu

Mauviel

2001

Journal of Biological Chemistry

Self Cite

611

472

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“…The cardiac temporal and spatial expression patterns for ␣1(VI), ␣2(VI), and ␣3(VI) chain transcripts were indistinguishable by in situ hybridization. These observations, coupled with our RPA analyses, are consistent with reports predicting that type VI collagen chains are usually expressed in a [1:1:1] stoichiometric ratio to form a [␣1(VI):␣2(VI):␣3(VI)] type VI collagen heterotrimer Heckmann et al, 1992).…”

Section: Resultssupporting

confidence: 78%

“…Type VI collagen, a heterotrimeric molecule composed of three polypeptide chains [␣1(VI), ␣2(VI), and ␣3(VI)], forms a microfibrillar extracellular network that interacts with basement membranes, fibrillar collagens, and other components of the ECM as well as with receptors at the cell surface (Van der Rest and Garrone, 1991;Brown and Timpl, 1995). Structural considerations predict that a 1:1:1 [␣1(VI): ␣2(VI): ␣3(VI)] type VI collagen chain assembly is required for the formation of a stable microfibrillar collagen network Heckmann et al, 1992). In vitro studies suggest type VI collagen, in its native state, participates in cell adhesion and migration through interactions with members of the integrin receptor family or the NG2 proteoglycan (Aumailley et al, 1989(Aumailley et al, , 1991Perris et al, 1993;Pfaff et al, 1993;Burg et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Expression of type VI collagen in the developing mouse heart

et al. 1998

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During development, the embryonic atrioventricular (AV) endocardial cushions undergo a morphogenic process to form mature valve leaflets and the membranous septa in the heart. Several extracellular matrix (ECM) proteins are expressed in the developing AV endocardial cushions, but it remains to be established if any specific ECM proteins are necessary for normal cushion morphogenesis. Abnormal development of the cardiac AV valves is a frequent cause of congenital heart defects, particularly in infants with trisomy 21 (Down syndrome). The genes encoding the α1 and α2 chains of type VI collagen are located on human chromosome 21 within the region thought to be critical for congenital heart defects in trisomy 21 infants. This suggests that the type VI collagen α1(VI) and α2(VI) chains may be important in normal AV valve morphogenesis. As a first step in understanding the role of type VI collagen in valve development, the authors examined the normal spatial and temporal expression patterns of mRNA and protein for type VI collagen in the embryonic mouse heart. Ribonuclease protection assay analysis demonstrates cardiac expression of the type VI collagen for α1(VI), α2(VI), and α3(VI) transcripts beginning at embryonic days 11–11.5 of mouse development. In situ hybridization studies demonstrate a coordinated pattern of cardiac expression within the AV valves for each type VI collagen chain from embryonic day 11.5 through the neonatal period. Immunohistochemical studies confirm a concentrated type VI collagen localization pattern in the endocardial cushions from the earliest stages of valve development through the neonatal period. These data indicate that type VI collagen is expressed in the developing AV canal in a pattern consistent with cushion tissue mesenchymal cell migration and proliferation, and suggest that type VI collagen plays a role in the morphogenesis of the developing cardiac AV endocardial cushions into the valve leaflets and membranous septa of the heart. Dev. Dyn. 1998;211:248–255. © 1998 Wiley‐Liss, Inc.

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“…Specifically, TGF-fl increases the synthesis of type VI collagen by dermal fibroblasts in culture. This effect is accompanied by an increase in ~3(VI) collagen mRNA levels whereas the levels of ~zl(VI) and c~2(VI) mRNAs remain unchanged upon TGF-fl stimulation [21]. These data suggest that the regulation of c~3(VI) collagen gene expression is critical for the control of collagen type VI synthesis.…”

Section: Resultsmentioning

confidence: 57%

Differential cytokine modulation of the genes LAMA3, LAMB3, and LAMC2, encoding the constitutive polypeptides, α3, β3, and γ2, of human laminin 5 in epidermal keratinocytes

1995

FEBS Letters

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Laminin 5, an anchoring filament protein previously known as niceinlkalinin/epiligrin, consists of three polypeptide chains, ¢~3, ~3, and ~2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. The expression of laminin 5 was detected by Northern hybridization with specific cDNA probes in various epidermal keratinocyte cultures, whereas no expression of any of the three genes could be detected in foreskin fibroblast cultures. Transforming growth factor-l~ (TGF-I~) enhanced LAMA3, LAMB3, and LAMC2 gene expression in human epidermal keratinocytes, as well as in HaCaT and BalblK cells in culture, although the extent of enhancement was greater for LAMA3 and LAMC2 genes than for LAMB3. Interestingly, tumor necrosis factor-a, (TNF-a) alone did not alter the expression of LAMB3 and LAMC2 genes in human epidermal keratinocytes, whereas it inhibited the expression of LAMA3. These results suggest that the expression of the three genes encoding the laminin 5 subunits is not coordinately regulated by the cytokines tested.

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Effect of transforming growth factors‐β on collagen type VI expression in human dermal fibroblasts

Cited by 37 publications

References 24 publications

Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach

Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach

Expression of type VI collagen in the developing mouse heart

Differential cytokine modulation of the genes LAMA3, LAMB3, and LAMC2, encoding the constitutive polypeptides, α3, β3, and γ2, of human laminin 5 in epidermal keratinocytes

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