Accelerated Healing of Incisional Wounds in Rats Induced by Transforming Growth Factor-β

Mustoe, Thomas A.; Pierce, Glenn F.; Thomason, Arlen; Gramates, Peggy; Sporn, Michael B.; Deuel, Thomas F.

doi:10.1126/science.2442813

Cited by 899 publications

(423 citation statements)

References 29 publications

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“…It is well recognized that addition of TGF-f to wound sites can accelerate the formation of new connective tissue (Sporn et al, 1983;Roberts et al, 1986;Mustoe et al, 1987). Furthermore, in a growth factor deficient healing-impaired animal model we developed based on adriamycin treatment, which lowers the circulating levels of platelet and leukocytes (Lawrence et al, 1986a), a single addition of TGF-f with PDGF and EGF on the day of surgery was sufficient to restore the repair process (Lawrence et al, 1986b).…”

Section: Discussionmentioning

confidence: 99%

Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

Igarashi

Okochi

Bradham

et al. 1993

MBoC

665

581

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Connective tissue growth factor (CTGF) is a cysteine-rich peptide that exhibits platelet-derived growth factor (PDGF)-like biological and immunological activities. CTGF is a member of a family of peptides that include serum-induced immediate early gene products, a v-src-induced peptide, and a putative avian transforming gene, nov. In the present study, we demonstrate that human foreskin fibroblasts produce high levels of CTGF mRNA and protein after activation with transforming growth factor beta (TGF-beta) but not other growth factors including PDGF, epidermal growth factor, and basic fibroblast growth factor. Because of the high level selective induction of CTGF by TGF-beta, it appears that CTGF is a major autocrine growth factor produced by TGF-beta-treated human skin fibroblasts. Cycloheximide did not block the large TGF-beta stimulation of CTGF gene expression, indicating that it is directly regulated by TGF-beta. Similar regulatory mechanisms appear to function in vivo during wound repair where there is a coordinate expression of TGF-beta 1 before CTGF in regenerating tissue, suggesting a cascade process for control of tissue regeneration and repair.

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Section: Discussionmentioning

confidence: 99%

Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

Igarashi

Okochi

Bradham

et al. 1993

MBoC

665

581

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“…These actions have been depicted in Figure 1. Of all cytokines, TGF-β is one of the most potent stimulators of ECM synthesis [13,14], and orchestrates ECM in normal tissue repair and remodelling [15,16]. However, it has been postulated that overproduction or persistent production of TGF-β leads to pathological deposition of ECM components, and eventually to scarring of renal tissue [17][18][19][20][21].…”

Section: Transforming Growth Factor-betamentioning

confidence: 99%

“…There is also evidence that PDGF is able to stimulate directly ECM synthesis [61]. PDGF has been described to play an important role in tissue repair and remodelling [15,16]. Besides its proliferative effects, PDGF recruits fibroblasts to sites of tissue injury.…”

Section: Eikmans Et Almentioning

confidence: 99%

ECM homeostasis in renal diseases: a genomic approach

Eikmans

Baelde

Heer

et al. 2003

The Journal of Pathology

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Chronic renal disease is in general histologically accompanied by a vast amount of scar tissue, ie glomerulosclerosis and interstitial fibrosis. Scarring results from excessive accumulation of extracellular matrix (ECM) components, a process driven by a plethora of cytokines and growth factors. Studies in experimental renal disease which target these regulators using gene therapy limit or prevent the development of scarring. This review focuses specifically on the role of transforming growth factor-beta, platelet-derived growth factor, connective tissue growth factor, hepatocyte growth factor, and epidermal growth factor. The results obtained in animal models hold promise for molecular intervention strategies in human renal disease. Microarray technology allows large-scale gene expression profiling in kidney tissue to identify common molecular pathways in a step towards discovery of new drug targets. Molecular techniques are expected to be used for diagnostic and prognostic purposes in nephrological practice to supplement renal biopsy. Several studies already show that molecular techniques might be of use in routine diagnostic practice. Improvement of diagnosis and prediction of outcome in renal patients might lead to more efficient and earlier therapeutic intervention.

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“…The growth factors that have been identified and isolated are, typically, specialized soluble proteins or polypeptides (McGrath, 1990;Ksander, 1989;Amento and Beck, 1991;Mustoe et al, 1987; Lynch et al, 1989;Bennett and Schultz, 1993). Thus, evidence of growth factors released at the site of trauma is extensive.…”

mentioning

confidence: 99%

Proliferative response of human and animal tumours to surgical wounding of normal tissues: onset, duration and inhibition

Bogden¹,

Moreau²,

Eden³

1997

Br J Cancer

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Summary Acceleration of secondary tumour growth and metastases following excision of a primary tumour has been attributed to the consequent removal of primary tumour-generated inhibitory factors. However, our studies have shown that surgical wounding of normal tissues significantly stimulated the growth of malignant tissues without the concomitant presence or excision of a tumour mass. A humoral stimulating component was indicated by the proliferative response of tumours and metastases distant from the surgical wound. All 16 human and murine tumours, of nine different histologies, showed a measurable acceleration of growth when implanted in surgically treated animals, suggesting that the ability of malignant tissue to respond to surgical wounding of normal tissue was not histologically or species specific. The proliferative surge of malignant tissues was detectable soon after wounding and had a duration of 2-3 days. The surgical wound as the source of the tumour-stimulating factor(s) was affirmed by the significant inhibition of tumour proliferative responses when a somatostatin analogue was applied topically to the surgical wound within 1 h of wounding, and/or during the critical tumour-stimulatory period of 1-2 days after wounding. A potential therapeutic window for reducing a risk factor that may be inadvertently imposed upon every surgical/oncology patient is indicated.Keywords: surgical wounding; wound-generated tumour growth factor; tumour proliferative response; lanreotide; normal tissue trauma Inhibition of tumour growth by tumour mass is a phenomenon recognized and repeatedly studied since the early 1900s (Ehrlich, 1908;Marie and Clunet, 1910;Tyzzer, 1913). Numerous reports, summarized more recently by Keller (1983) and O'Reilly et al (1994), have indicated that the presence of a primary tumour inhibits the growth rate of metastases or of a second tumour implant, and that removal or eradication of the primary tumour accelerates growth at secondary sites. Early explanations for apparent exacerbations of disease reflected Ehrlich's hypothesis of 'Athrepsia'; that any actively growing tumour removed certain specific nutritive material necessary for growth from the host animal (Ehrlich and Apolant, 1905). Subsequent explanations stressed surgical relief from growth-limiting factors, such as anatomical boundaries, anoxia and nutritional deficiencies, or that the immunological relation between host and tumour was somehow altered by surgery, thereby facilitating tumour escape. However, the underlying cause of the occasional explosive metastatic manifestation after resection of 'primary' malignancy remained in question. An alternative explanation, proposed by Keller (1983) inhibitor (angiostatin). They postulated that a primary tumour, while capable of stimulating angiogenesis in its own vascular bed by generating angiogenic stimulators in excess of angiogenesis inhibitors, the angiogenesis inhibitor, by virtue of its longer halflife in the circulation, reaches the vascular bed of a secondary tumour in excess o...

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Accelerated Healing of Incisional Wounds in Rats Induced by Transforming Growth Factor-β

Cited by 899 publications

References 29 publications

Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

ECM homeostasis in renal diseases: a genomic approach

Proliferative response of human and animal tumours to surgical wounding of normal tissues: onset, duration and inhibition

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