Collagenase gene expression in fibroblasts is regulated by a three‐dimensional contact with collagen

Mauch, Cornelia; Adelmann-Grill, B. C.; Hatamochi, Atsushi; Krieg, Thomas

doi:10.1016/0014-5793(89)80743-4

Cited by 111 publications

(64 citation statements)

References 32 publications

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“…This was characterized by the presence of organized stress fibers within the cytoskeleton and an up-regulation of the anabolic gene (al(1) collagen). Loss of cytoskeletal organization through chemical disruption or a detachment of the gel resulted in an upregulation in the expression of the catabolic gene (interstitial collagenase) and an inhibition in the expression of the anabolic gene (al (1) [33,40,41,43,56].…”

Section: Discussionmentioning

confidence: 99%

In vitro alterations in cytoskeletal tensional homeostasis control gene expression in tendon cells

Lavagnino

Arnoczky

2005

Journal Orthopaedic Research

128

137

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An in vitro collagen gel system was used to determine the effect of alterations in cytoskeletal tensional homeostasis on gene expression in tendon cells. Collagen gel matrices, seeded with rat tail tendon cells, underwent cytochalasin D and gel contraction treatments designed to alter the internal cytoskeletal homeostasis of the cells. Gels were examined for cytoskeletal organization using a rhodamine phalloidin stain for actin. The effect of altered cytoskeletal organization on mRNA expression of a catabolic (interstitial collagenase) and anabolic (ul (I) collagen) gene was examined using northern blot analysis. Tendon cells in adhered gels demonstrated a highly organized cytoskeleton and showed evidence of ul (I) collagen mRNA expression but no evidence of collagenase mRNA expression. Treatment of the attached gel with cytochalasin D disrupted the cytoskeletal organization and resulted in the upregulation of collagenase mRNA and the inhibition of ul(1) collagen mRNA expression. Release of the gels resulted in a cell mediated gel contraction, an immediate loss of cytoskeletal organization, and an mRNA expression pattern similar to that seen with cytochalasin D treatment. Isometric contraction of the gel on itself or around a 3-point traction device resulted in an mRNA expression pattern similar to the adhered gel. Gene expression in the contracted gels could be reversed through chemical cytoskeletal disruption or removal of the traction device which permitted further gel contraction. The results of the study suggest that tendon cells can establish an internal cytoskeletal tension through interactions with their local extracellular environment. Alterations in this tension appear to control the expression of both catabolic and anabolic genes in a reciprocal manner.

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Section: Discussionmentioning

confidence: 99%

In vitro alterations in cytoskeletal tensional homeostasis control gene expression in tendon cells

Lavagnino

Arnoczky

2005

Journal Orthopaedic Research

128

137

View full text Add to dashboard Cite

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“…On the basis of studies showing that MMP-1 expression similarly depends on the mechanical signals by three-dimensional collagen lattices [22] and that integrin α # β " mediates both p38α activation [19] and MMP-1 expression induced by threedimensional collagen lattices [33], we hypothesized that p38α activation and MMP-1 expression might be related. To our surprise, the inhibition of p38α by SB203580 resulted in the bipolar pattern of MMP-1 expression induced by fl-coll (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have also reported that the p38 MAPK is required for the induction of MMP-1 gene expression by ceramide and tumour-derived extracellular matrix metalloproteinase inducer (EMMPRIN) [20,21]. Interestingly, although contracting collagen lattices induce both activation of p38 MAPK [18] and expression of MMP-1 [3,22] in human fibroblasts, the complete inhibition of p38 MAPK by SB203580 at 10 µM does not result in appreciable suppression of MMP-1 expression [18].…”

Section: Introductionmentioning

confidence: 99%

p38 mitogen-activated kinase is a bidirectional regulator of human fibroblast collagenase-1 induction by three-dimensional collagen lattices

Clark

Parks

2001

Biochem. J.

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When fibroblasts are cultured in contracting collagen matrices, matrix metalloproteinase-1 (MMP-1, collagenase-1) is induced. In the present study we demonstrate that p38α mitogen-activated protein kinase (p38α MAPK) plays a bi-directional role in the MMP-1 response to contracting floating collagen lattices (flcoll). fl-coll, but not attached collagen lattices (att-coll), coordinately increased expression of MMP-1 and activities of p38α and MKK3\6 (MAPK kinase 3\6). However, treatment of primary fibroblasts cultured in fl-coll with increasing doses of SB203580, an inhibitor of p38α and p38β, caused a bipolar pattern of MMP-1 expression. Partial inhibition of p38 MAPK activity resulted in the lowest level of MMP-1 expression, whereas total inhibition of p38 activity led to MMP-1 levels as high as in the absence of inhibitor. The activation\inhibition of p38α was apparently responsible for the observed phenomena, as supported by three lines of evidence. (1) p38α was the predominant isoform sensitive to SB203580 in primary fibroblasts. (2) Fibroblasts transfected with increasing dose of a dominant negative p38α

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“…Alternatively, the parameters that the two assays measure may be distinct. Cell invasion into collagen matrices is likely to be a more complex phenomenon than locomotion across a planar substrate, in terms of (i) cell-matrix interactions, (ii) actin cytoskeletal rearrangements in three-dimensions, (iii) modulation of intracellular signaling by a 3D collagen matrix (Roeckel and Krieg, 1994;Xu and Clark, 1997), and (iv) invasion and degradation of collagen (Mauch et al, 1989), and these dierences may explain the additional requirement for Cdc42 and Rho activity.…”

Section: Differential Signals In Motility and Invasionmentioning

confidence: 99%

Motility and invasion are differentially modulated by Rho family GTPases

et al. 2000

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Cell migration in vivo often requires invasion through tissue matrices. Currently little is known regarding the signaling pathways that regulate cell invasion through three-dimensional matrices. The small GTPases Cdc42, Rac and Rho are key regulators of actin cytoskeletal and adhesive structures. We now show that expression of dominant negative forms of either Cdc42, Rac or Rho inhibited PDGF-BB-stimulated Rat1 ®broblast invasion into 3D collagen matrices, indicating that the activity of each of these GTPases is necessary for cell invasion. In contrast, only Rac activation was required for PDGF-BB-stimulated locomotion across a planar substrate in the Boyden chamber. Interestingly, PDGF-induced invasion was also strongly inhibited by expression of constitutively active forms of Cdc42 or Rho, and to a lesser extent by constitutively active Rac. We also show that constitutively active V12-Rac signi®cantly stimulated basal Rat1 ®broblast invasion, independent of PI-3-kinase activity, and that this eect was suppressed by the eector mutant V12/H40-Rac. These results suggest that cellular invasion may require an optimal level of activation of Cdc42, Rho and Rac, and that migration and invasion are dierentially modulated by Rho family GTPases. Oncogene (2000) 19, 580 ± 591.

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Collagenase gene expression in fibroblasts is regulated by a three‐dimensional contact with collagen

Cited by 111 publications

References 32 publications

In vitro alterations in cytoskeletal tensional homeostasis control gene expression in tendon cells

In vitro alterations in cytoskeletal tensional homeostasis control gene expression in tendon cells

p38 mitogen-activated kinase is a bidirectional regulator of human fibroblast collagenase-1 induction by three-dimensional collagen lattices

Motility and invasion are differentially modulated by Rho family GTPases

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