Fibroblasts from wounds of different stages of repair vary in their ability to contract a collagen gel in response to growth factors

Finesmith, Tina H.; Broadley, Kenneth N.; Davidson, Jeffrey M.

doi:10.1002/jcp.1041440113

Cited by 108 publications

(65 citation statements)

References 29 publications

(40 reference statements)

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“…Among cytokines implicated in myofibroblast differentiation, TGF␤ has been proven to directly induce ␣-SMA expression in vivo and in vitro (Desmoulière et al, 1993;Rønnov-Jessen and Petersen, 1993). A series of studies with the use of free-floating collagen gels reported TGF␤-induced fibroblast contraction, but did not consider the expression of ␣-SMA (Montesano and Orci, 1988;Finesmith et al, 1990;Tingstrom et al, 1992;Pena et al, 1994;Riikonen et al, 1995;Levi-Schaffer et al, 1999) with two exceptions (Arora and McCulloch, 1994;Kurosaka, 1995;2154). However, it was shown recently that the mechanisms of mechanically unloaded free-floating gel reduction considerably differ from stressed gel contraction (for review see Grinnell, 2000).…”

Section: Discussionmentioning

confidence: 99%

Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity

Hinz

Celetta

Tomasek³

et al. 2001

MBoC

1,117

947

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To evaluate whether ␣-smooth muscle actin (␣-SMA) plays a role in fibroblast contractility, we first compared the contractile activity of rat subcutaneous fibroblasts (SCFs), expressing low levels of ␣-SMA, with that of lung fibroblasts (LFs), expressing high levels of ␣-SMA, with the use of silicone substrates of different stiffness degrees. On medium stiffness substrates the percentage of cells producing wrinkles was similar to that of ␣-SMA-positive cells in each fibroblast population. On high stiffness substrates, wrinkle production was limited to a subpopulation of LFs very positive for ␣-SMA. In a second approach, we measured the isotonic contraction of SCF-and LF-populated attached collagen lattices. SCFs exhibited 41% diameter reduction compared with 63% by LFs. TGF␤1 increased ␣-SMA expression and lattice contraction by SCFs to the levels of LFs; TGF␤-antagonizing agents reduced ␣-SMA expression and lattice contraction by LFs to the level of SCFs. Finally, 3T3 fibroblasts transiently or permanently transfected with ␣-SMA cDNA exhibited a significantly higher lattice contraction compared with wild-type 3T3 fibroblasts or to fibroblasts transfected with ␣-cardiac and ␤-or ␥-cytoplasmic actin. This took place in the absence of any change in smooth muscle or nonmuscle myosin heavy-chain expression. Our results indicate that an increased ␣-SMA expression is sufficient to enhance fibroblast contractile activity. INTRODUCTIONEarly during healing of an open wound, resident dermal fibroblasts proliferate from the wound margin and migrate into the provisional matrix composed of a fibrin clot. About 1 week after wounding, the provisional matrix is replaced by neo-formed connective tissue, known as granulation tissue, essentially composed of small vessels, extracellular matrix, and fibroblastic cells that become activated and modulate into myofibroblasts. The main feature of myofibroblasts is represented by an important contractile apparatus similar to that of smooth muscle (Gabbiani et al., 1971), and in particular by the neo-expression of ␣-smooth muscle actin (␣-SMA), the actin isoform typical of vascular smooth muscle cells (Skalli et al., 1986). Myofibroblasts are recognized to play a central role in closing the wound tissue, through their capacity to produce a strong contractile force (for review see Grinnell, 1994;Rønnov-Jessen et al., 1996;Powell et al., 1999;Serini and Gabbiani, 1999), possibly generated within stress fibers, similar to those present in cultured fibroblasts (Skalli et al., 1986;Serini and Gabbiani, 1999). Because wound contraction takes place when de novo expressed ␣-SMA is incorporated in stress fibers (Darby et al., 1990), it has been suggested that this actin isoform plays an important role in granulation tissue contraction (for review see Serini and Gabbiani, 1999). Although stress fibers have been proposed to function as contractile organelles (Burridge, 1981;Katoh et al., 1998) and their presence has been correlated with the production of isometric tension (Harris et al., 1981), at p...

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Section: Discussionmentioning

confidence: 99%

Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity

Hinz

Celetta

Tomasek³

et al. 2001

MBoC

1,117

947

View full text Add to dashboard Cite

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“…In vitro, TGF-β1 reduces the collagenase-mediated degradation of the wound matrix and indirectly stimulates matrix growth by inducing platelet-derived growth factor [17,20,21]. TGF-β1 enhances the contraction of collagen gel and thus of the wound itself [22][23][24]. An important role of TGF is underpinned by the fact that neutralizing antibodies to TGF inhibit hypertrophic scar formation [17,[25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Differences in Hypertrophic Scar Fibroblasts according to Scar Severity: Expression of Transforming Growth Factor β1 at the mRNA and Protein Levels

Kim

Nam

Park

et al. 2015

Arch Aesthetic Plast Surg

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“…In contrast to the inhibitory effects of pro-inflammatory cytokines, a number of growth factors including fibroblast growth factor (FGF), platelet derived growth factor (PDGF), transforming growth factor beta (TGF-β), and insulin-like growth factor (IGF) have been shown to stimulate a healing response in articular cartilage [38], wound granulation [39], and ligament [40].…”

Section: Cell Biology and Meniscal Healing: Cytokines And Growth Factorsmentioning

confidence: 99%

Augmentation techniques for isolated meniscal tears

Taylor

Rodeo

2013

Curr Rev Musculoskelet Med

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Meniscal tears are relatively common injuries sustained by athletes and non-athletes alike and have far reaching functional and financial implications. Studies have clearly demonstrated the important biomechanical role played by the meniscus. Long-term follow-up studies of post-menisectomy patients show a predisposition toward the development of degenerative arthritic changes. As such, substantial efforts have been made by researchers and clinicians to understand the cellular and molecular basis of meniscal healing. Proinflammatory cytokines have been shown to have a catabolic effect on meniscal healing. In vitro and some limited in vivo studies have shown a proliferative and anabolic response to various growth factors. Surgical techniques that have been developed to stimulate a healing response include mechanical abrasion, fibrin clot application, growth factor application, and attempts at meniscal neovascularization. This article discusses various augmentation techniques for meniscal repair and reviews the current literature with regard to fibrin clot, platelet rich plasma, proinflammatory cytokines, and application of growth factors.

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Fibroblasts from wounds of different stages of repair vary in their ability to contract a collagen gel in response to growth factors

Cited by 108 publications

References 29 publications

Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity

Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity

Differences in Hypertrophic Scar Fibroblasts according to Scar Severity: Expression of Transforming Growth Factor β1 at the mRNA and Protein Levels

Augmentation techniques for isolated meniscal tears

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