Fibroblast contraction of collagen lattices in vitro: Inhibition by chronic inflammatory cell mediators

Hp, Ehrlich; Dj, Wyler

doi:10.1002/jcp.1041160312

Cited by 107 publications

(54 citation statements)

References 13 publications

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“…#P Ͻ 0.01. (9). Taken together, these data suggest that a dynamic, reciprocal relationship exists between epithelial cell migration and ECM fibronectin deposition such that ECM remodeling is downregulated after fibronectinmediated reepithelialization of the airways.…”

Section: Discussionmentioning

confidence: 73%

Fibronectin matrix polymerization regulates small airway epithelial cell migration

Hocking

Chang

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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The continuous conversion of soluble fibronectin into extracellular matrix fibrils occurs through a dynamic, cell-dependent process. As the extracellular matrix is assembled, changes in the conformation of matrix proteins may expose biologically active, matricryptic sites that alter cell behavior. In this study, an in vitro model of wound healing was used to determine the role of matrix fibronectin in airway epithelial cell motility. Our findings indicate that, under basal conditions, small airway epithelial cell (SAEC) migration requires active fibronectin matrix polymerization. Furthermore, SAEC migration is increased significantly by the interaction of cells with a recombinant construct containing fibronectin's matricryptic III-1 site. In contrast, addition of increasing amounts of fibronectin to SAECs significantly decreased the rate of cell migration. This fibronectin-induced inhibition of cell migration was overcome by blocking excess fibronectin matrix deposition. These data indicate that SAEC migration is regulated in a biphasic manner by the polymerization of fibronectin in the extracellular matrix and suggest a stimulatory role for fibronectin's matricryptic III-1 site in cell motility.

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Section: Discussionmentioning

confidence: 73%

Fibronectin matrix polymerization regulates small airway epithelial cell migration

Hocking

Chang

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…PGE is a well-established inhibitor of several fibroblast repair responses, including chemotaxis (18,46), proliferation (47,48), production of extracellular matrix macromolecules (48), and contraction of three-dimensional collagen gels (16,17). The current study evaluated only chemotaxis and contraction, but it seems likely that PGE may also contribute to the reduced proliferation noted in fibroblasts from patients with COPD.…”

Section: Discussionmentioning

confidence: 94%

“…Increased production of PGE 2 , a known inhibitor of both gel contraction and chemotaxis (16)(17)(18), accounts for part of the reduced activity of fibroblasts from subjects with COPD. Consistent with the increased production of PGE, fibroblasts from subjects with COPD have increased expression of COX1 and COX2, two enzymes that regulate the production of prostaglandins in fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Lung Fibroblast Repair Functions in Patients with Chronic Obstructive Pulmonary Disease Are Altered by Multiple Mechanisms

Togo¹,

Holz²,

Liu

et al. 2008

Am J Respir Crit Care Med

170

178

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Rationale: Fibroblasts are believed to be the major cells responsible for the production and maintenance of extracellular matrix. Alterations in fibroblast functional capacity, therefore, could play a role in the pathogenesis of pulmonary emphysema, which is characterized by inadequate maintenance of tissue structure. Objectives: To evaluate the hypothesis that deficient fibroblast repair characterizes cells obtained from individuals with chronic obstructive pulmonary disease (COPD) compared with control subjects. Methods: Fibroblasts were cultured from lung tissue obtained from individuals undergoing thoracotomy and were characterized in vitro. Measurements and Main Results: Fibroblasts from individuals with COPD, defined by reduced FEV 1 , manifested reduced chemotaxis toward fibronectin and reduced contraction of three-dimensional collagen gels, two bioassays associated with fibroblast repair function. At least two mechanisms appear to account for these differences. Prostaglandin E (PGE), a known inhibitor of fibroblast repair functions, was produced in increased amount by fibroblasts from subjects with COPD, which also expressed increased amounts of the receptors EP2 and EP4, both of which signal through cyclic AMP. Incubation of fibroblasts with indomethacin or with the PKA inhibitor KT-5720 partially restored COPD subject fibroblast function. In addition, fibroblasts from subjects with COPD produced more transforming growth factor (TGF)-b1, but manifested reduced response to TGF-b1. The functional alterations in fibroblasts correlated with both lung function assessed by FEV 1 and, for the data available, with severity of emphysema assessed by DL CO . Conclusions: Fibroblasts from individuals with COPD have reduced capability to sustain tissue repair, which suggests that this may be one mechanism that contributes to the development of emphysema.

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“…The number of human foreskin fibroblasts and 3T3-L1 cells contained within collagen gels, whether in the presence or absence of TGF-, showed no significant change during the course of the Medical Sciences: Montesano (18)(19)(20)(21)(22) have shown that fibroblasts incorporated into three-dimensional collagen gels induce a progressive contraction of the gels and that this phenomenon requires the presence of serum. We have demonstrated here that TGF-pB substitutes for serum in stimulating fibroblast contraction of collagen gels and markedly enhances the contraction normally observed in the presence of serum.…”

Section: Resultsmentioning

confidence: 99%

“…This phenomenon has been considered as an in vitro equivalent of the connective-tissue contraction that occurs during wound healing and other biological processes (18)(19)(20)(21)(22), and it provides a simple method ofquantitating the contractile ability offibroblasts. Using this model, we have found that TGF-P powerfully enhances the ability of fibroblasts to contract a collagen matrix.…”

mentioning

confidence: 99%

Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing.

Montesano

Orci

1988

Proc. Natl. Acad. Sci. U.S.A.

487

333

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An important event during wound healing is the contraction of newly formed connective tissue (granulation tissue) by fibroblasts. The role of polypeptide growth factors in the process of wound contraction was investigated by analyzing the influence of transforming growth factor (3 (TGF-(3), platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor on the ability of fibroblasts to contract a collagen matrix in an in vitro system. TGF-J3, but not the other growth factors tested, markedly enhanced the ability of BHK-21, 3T3-L1, and human foreskin fibroblasts to contract collagen gels. These results suggest that TGF-P released from platelets and inflammatory cells at sites of tissue injury stimulates fibroblasts to contract the provisional wound matrix and that this effect contributes to the ability of TGF-13 to accelerate wound healing.The process of wound repair involves an ordered sequence of events. Inflammatory cells first migrate into the plasma clot, followed by fibroblasts, which elaborate collagen and other matrix components (1) and which eventually contract the newly formed connective tissue to bring together the edges of the wound (2-4). Polypeptide growth factors are thought to play important roles in tissue repair (5). Transforming growth factor f3 (TGF-(3) is a multifunctional regulatory polypeptide present in a wide variety of tissues and is especially abundant in platelets, from which it is released at sites of injury (6). Experimental work with animal models has demonstrated that TGF-P (7-9), in concert with other growth factors (7, 10-12), can promote wound healing. In vitro studies suggested that stimulation of wound healing by TGF-,l may result from the ability of the growth factor to regulate crucial steps in the repair process. Thus, TGF-,B has been shown to be chemotactic for inflammatory cells (13) and for fibroblasts (14) and to induce fibroblasts to produce increased amounts of collagen and fibronectin (8,(15)(16)(17). Whether TGF-,B also plays a role in the contraction of the provisional wound matrix is not known.In 1979, Bell et al. (18) Ag/ml).Three-dimensional collagen gels were prepared essentially as described (23). In brief, type I collagen was extracted by stirring adult rat tail tendons for 48 hr at 40C in a sterile 0.1% (vol/vol) acetic acid solution (300 ml for 1 g of collagen). The resulting solution was centrifuged at 16,000 x g for 1 hr at 40C. The supernatant was then extensively dialyzed against 0.1 x MEM and stored at 40C. For incorporation into collagen gels, cells were harvested from confluent cultures by using 0.05% trypsin/0.02% EDTA, counted, adjusted to the desired density, and centrifuged in a plastic tube. The tube was placed on ice, and the cell pellet was resuspended in a solution of polymerizing collagen, which was prepared by quickly mixing 8 volumes of collagen stock solution with 1 volume of 10 x concentrated MEM and 1 volume of sodium bicarbonate (11.76 mg/ml). Aliquots (2 ml) of the cold collagen mixture were dispensed in...

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Fibroblast contraction of collagen lattices in vitro: Inhibition by chronic inflammatory cell mediators

Cited by 107 publications

References 13 publications

Fibronectin matrix polymerization regulates small airway epithelial cell migration

Fibronectin matrix polymerization regulates small airway epithelial cell migration

Lung Fibroblast Repair Functions in Patients with Chronic Obstructive Pulmonary Disease Are Altered by Multiple Mechanisms

Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing.

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