Human Wound Healing Fibroblasts Have Greater Contractile Properties Than Dermal Fibroblasts

Germain, Lucie; Jean, Andréa; Auger, François A.; Garrel, Dominique R.

doi:10.1006/jsre.1994.1143

Cited by 98 publications

(63 citation statements)

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“…In conclusion, fetal and postnatal sera differentially (Skalli et al, 1988;Germain et al, 1994) and that gel contraction is dependent on a-SM actin expression (Ar-modulate human dermal fibroblast phenotype and ora et al, 1994). As mentioned earlier, myofibroblasts functional features in vitro.…”

Section: Collagen Synthesismentioning

confidence: 94%

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Fetal and postnatal sera differentially modulate human dermal fibroblast phenotypic and functional features in vitro

et al. 1997

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Fetal wounds heal without scar formation, fibrosis, or contracture. Compared with adult wounds, they are characterized by major differences in the extracellular matrix and the absence of myofibroblastic cells. The reasons for these differences are not well known and determination of factors affecting the absence of scarring in the fetus may lead to strategies for controlling adult pathological scarring. In the present study, we have assessed the effects of serum on the behavior of normal human dermal fibroblasts. Using an in vitro approach, we investigated the effects of fetal and adult serum on cell properties such as growth rate, collagen synthesis, gelatinase activities, and differentiation to myofibroblasts using biochemical, morphological, and ultrastructural parameters. We studied the induction of alpha-smooth muscle (alpha-SM) actin in fibroblasts, and its correlation with increased collagen gel contraction by the cells. Our results showed that, compared with FBS (fetal bovine serum), postnatal calf serum (PCS) decreased mitogenic activity and collagenase synthesis but not collagen synthesis. Furthermore, cells cultured with PCS differentiated to myofibroblasts with an increase in cell diameter, number of stress fibers, alpha-SM actin expression, and collagen gel contraction. To characterize the molecules involved in this differentiation process, the amount of transforming growth factor beta (TGFbeta) in FBS and PCS was determined and the effect of neutralizing anti-TGFbeta antibody was evaluated. It was determined that FBS contained more TGFbeta than PCS, but that essentially all the TGFbeta was latent in both sera. However, results obtained with anti-TGFbeta antibody show that active TGFbeta is present when human dermal fibroblasts are cultured with medium containing PCS. These results suggest that, in the presence of PCS but not FBS, the cells either produce active TGFbeta or an enzyme that is able to activate latent serum TGFbeta. Alternatively, sera may contain two different forms of latent TGFbeta, the PCS form being activated by the dermal fibroblast cells. A similar mechanism may be involved, at least in part, in skin wound healing and may underlie the appearance of myofibroblasts in postnatal wounds.

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Section: Collagen Synthesismentioning

confidence: 94%

“…TGFb1 was coupled to keyhole limpet hemocyanin et al, 1972;Germain et al, 1994). Environmental factors also seem to contribute to the fundamental differences (KLH) in the following manner.…”

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confidence: 96%

Fetal and postnatal sera differentially modulate human dermal fibroblast phenotypic and functional features in vitro

et al. 1997

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“…Wounding leads initially to the formation of a fibrin-rich plug, followed by the accumulation of leukocytes and the migration of αSMA + myofibroblasts from adjacent dermis and underlying adipose tissue into the wound (75)(76)(77)(78). Subsequently, the infiltrating αSMA + fibroblasts develop a contractile phenotype (79). Lineage tracing in the mouse demonstrates that the initial wave of fibroblast migration is derived from lower-lineage (i.e., reticular) fibroblasts (56).…”

Section: Extrinsic Factors Governing Fibroblast Cellular Identitymentioning

confidence: 99%

Fibroblast heterogeneity: implications for human disease

Lynch

Watt

2018

Journal of Clinical Investigation

366

294

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“…A better understanding of the process of force generation and cell-matrix attachment is essential to understanding regulation of the process. The mechanism of contraction has been studied extensively using 3-dimensional Fibroblast Populated Collagen Lattices (FPCL), which model some of the in vivo events [Elsdale and Bard, 1972;Bell et al, 1979;Ehrlich and Rajaratnam, 1990;Asaga et al, 1991;Germain et al, 1994]. Direct measurements of the forces generated have been made on tethered forms of FPCLs [Delvoye et al, 1991;Kolodney and Wysolmerski, 1992] including the defined quantitative model, the Culture Force Monitor (CFM) [Eastwood et al, 1994.…”

Section: Introductionmentioning

confidence: 99%

Contraction‐mediated pinocytosis of RGD‐peptide by dermal fibroblasts: Inhibition of matrix attachment blocks contraction and disrupts microfilament organisation

Sethi

Mudera

Sütterlin

et al. 2002

Cell Motil. Cytoskeleton

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Force generation in collagen and matrix contraction are basic functions of fibroblasts and important elements of tissue repair. Cell-matrix attachment is critical to this contraction, involving RGD-binding integrins. We have investigated how this process operates, in terms of force generation (in the Culture Force Monitor) and cytoskeletal structure, using a synthetic RGD-decapeptide. The RGD-peptide blocked force generation over the first 6 h, followed by near complete recovery by 20 h. However, dose response was complex indicating multiple processes were operating. Analysis of cytoskeletal structure after treatment with RGD-peptide indicated major disruption with condensed aggregates of actin and microtubular fragmentation. Fluorescent labeling and tracking of the RGD-peptide demonstrated intracellular uptake into discrete cytoplasmic aggregates. Critically, these RGD-peptide pools co-localised with the condensed actin microfilament aggregates. It is concluded that RGD-peptide uptake was by a form of contraction-mediated pinocytosis, resulting from mechanical tension applied to the untethered RGD-peptide-integrin, as contractile microfilament were assembled. These findings emphasize the importance of sound mechanical attachment of ligand-occupied integrins (e.g., to extracellular matrix) for normal cytoskeletal function. Conversely, this aspect of unrestrained cytoskeletal contraction may have important pathogenic and therapeutic applications.

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Human Wound Healing Fibroblasts Have Greater Contractile Properties Than Dermal Fibroblasts

Cited by 98 publications

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Fetal and postnatal sera differentially modulate human dermal fibroblast phenotypic and functional features in vitro

Fetal and postnatal sera differentially modulate human dermal fibroblast phenotypic and functional features in vitro

Fibroblast heterogeneity: implications for human disease

Contraction‐mediated pinocytosis of RGD‐peptide by dermal fibroblasts: Inhibition of matrix attachment blocks contraction and disrupts microfilament organisation

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