Incisional wound healing in transforming growth factor‐β1 null mice

Koch, Rafael; Roche, Nanette S.; Parks, W. Tony; Ashcroft, Gillian S.; Letterio, John J.; Roberts, Anita B.

doi:10.1046/j.1524-475x.2000.00179.x

Cited by 80 publications

(57 citation statements)

References 52 publications

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“…Indeed, the use of genetically modified mice for wound healing studies recently revealed crucial roles for several growth factors and cytokines in the repair process (Table 4). For example, these studies have demonstrated an inhibitory effect of TGF-␤ on wound reepithelialization (2,12,66,149), an important role of FGF receptor signaling in this process (292), and a role of activin in granulation tissue formation and scarring (192,286). In the latter case, the phenotype was more pronounced in a CD1 background compared with a B6D2F2 background (Werner, unpublished data), demonstrating the importance of the genetic background for the outcome of the repair process.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Wound Healing by Growth Factors and Cytokines

Werner

Grose

2003

Physiological Reviews

3,058

2,082

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Werner, Sabine, and Richard Grose. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol Rev 83: 835–870, 2003; 10.1152/physrev.00032.2002.—Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process.

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Section: Discussionmentioning

confidence: 99%

Regulation of Wound Healing by Growth Factors and Cytokines

Werner

Grose

2003

Physiological Reviews

3,058

2,082

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“…Many animal models of impaired wound healing have shown that reduction of endogenous TGF-␤1 in the wound bed underlies the defective repair process. This concept, however, has recently been questioned, because TGF-␤1 -/-and Smad3 -/-null mice showed accelerated wound healing and a reduction in the area of granulation tissue (Ashcroft et al, 1999;Koch et al, 2000). The findings may be explained in terms of the function of different TGF-␤ isoforms (O'Kane and Ferguson, 1997).…”

Section: (D) Wound Healingmentioning

confidence: 99%

TGF-β Signal Transduction in Oro-facial Health and Non-malignant Disease (Part I)

Prime

Pring

Davies

et al. 2004

Critical Reviews in Oral Biology & Medicine

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ABSTRACT:The transforming growth factor-beta (TGF-␤) family of cytokines consists of multi-functional polypeptides that regulate a variety of cell processes, including proliferation, differentiation, apoptosis, extracellular matrix elaboration, angiogenesis, and immune suppression, among others. In so doing, TGF-␤ plays a key role in the control of cell behavior in both health and disease. In this report, we review what is known about the mechanisms of activation of the peptide, together with details of TGF-␤ signal transduction pathways. This review summarizes the evidence implicating TGF-␤ in normal physiological processes of the craniofacial complex-such as palatogenesis, tooth formation, wound healing, and scarring-and then evaluates its role in non-malignant disease processes such as scleroderma, submucous fibrosis, periodontal disease, and lichen planus.

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“…However, in vivo data do not fully support such a stimulatory role of TGF-β signalling. Thus, mouse null mutants for Tgfb1 or the TGF-β-regulated transcription factor Smad3 show accelerated, rather than impaired wound closure (Ashcroft et al, 1999;Koch et al, 2000). This paradoxical result has been proposed to be due to concomitant and predominant effects of TGF-β signalling to suppress keratinocyte proliferation, which might counteract a direct stimulatory effect on epidermal migration (Ashcroft et al, 1999;Barrientos et al, 2008;Sivamani et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Re-epithelialization of cutaneous wounds in adult zebrafish uses a combination of mechanisms at play during wound closure in embryonic and adult mammals

et al. 2016

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Re-epithelialization of cutaneous wounds in adult mammals takes days to complete and relies on numerous signalling cues and multiple overlapping cellular processes that take place both within the epidermis and in other participating tissues. Re-epithelialization of partial-or fullthickness skin wounds of adult zebrafish, however, is extremely rapid and largely independent of the other processes of wound healing. Live imaging after treatment with transgene-encoded or chemical inhibitors reveals that re-epithelializing keratinocytes repopulate wounds by TGF-β-and integrin-dependent lamellipodial crawling at the leading edges of the epidermal tongue. In addition, re-epithelialization requires long-range epithelial rearrangements, involving radial intercalations, flattening and directed elongation of cells -processes that are dependent on Rho kinase, JNK and, to some extent, planar cell polarity within the epidermis. These rearrangements lead to a massive recruitment of keratinocytes from the adjacent epidermis and make reepithelialization independent of keratinocyte proliferation and the mitogenic effect of FGF signalling, which are only required after wound closure, allowing the epidermis outside the wound to re-establish its normal thickness. Together, these results demonstrate that the adult zebrafish is a valuable in vivo model for studying and visualizing the processes involved in cutaneous wound closure, facilitating the dissection of direct from indirect and motogenic from mitogenic effects of genes and molecules affecting wound re-epithelialization.

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Incisional wound healing in transforming growth factor‐β1 null mice

Cited by 80 publications

References 52 publications

Regulation of Wound Healing by Growth Factors and Cytokines

Regulation of Wound Healing by Growth Factors and Cytokines

TGF-β Signal Transduction in Oro-facial Health and Non-malignant Disease (Part I)

Re-epithelialization of cutaneous wounds in adult zebrafish uses a combination of mechanisms at play during wound closure in embryonic and adult mammals

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