Expression of Transforming Growth Factor Beta 1, 2, and 3 Proteins in Keloids

Lee, Thomas Y.; Chin, Gyu S.; Kim, William J. H.; Chau, Dorothy; Gittes, George K.; Longaker, Michael T.

doi:10.1097/00000637-199943020-00013

Cited by 165 publications

(95 citation statements)

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“…Other isoforms of TGF-P, such as TGF-P2 and P3, were reported to be endogenously produced and cause posttraumatic fibrosis in human skin [18], pancreas [7], and blood vessels [32] during the reparative procedure after these organs were damaged. Platelet derived growth factor-AB was also reported to cause kidney fibrosis in conjunction with TGF-PI [15].…”

Section: Discussionmentioning

confidence: 99%

Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor‐β1

Nakatani

Marui

Hitora

et al. 2002

Journal Orthopaedic Research

133

125

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Although mechanical stress as a result of spinal instability is known to cause hypertrophy of the ligameiitum flavum resulting in degenerative spinal canal stenosis, the mechanism of the ligament hypertrophy is not well understood. In the present study, we investigated the effect of mechanical stretching force on collagen synthesis and transforming growth factor-/3 1 (TGF-PI) production using ligament cells isolated from human ligamentum flavum in vitro. Ligamenturn flavum cells (LFCs) were isolated from human ligamenturn flavum obtained from patients who underwent lumbar spine surgery. The LFCs were subjected to a mechanical stretching force using a cominercially available stretching device that physically deformed the cells. Collagen synthesis and TGF-PI production levels in the LFCs were then examined. Notable increases were observed in the gene expressions of collagen types I, 111, and V in LFCs subjected to mechanical stretching force. The increase in collagen gene expression of LFCs was inhibited in the presence of anti-TGF-pl antibodies. Production of TGF-PI by the LFCs also increased significantly by the mechanical stretching force. Exogenous application of TGF-PI was confirmed to increase collagen synthesis of the LFCs. This data indicated that mechanical stretching force can promote TGF-Dl production by LFCs, resulting in hypertrophy of the ligament.

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Section: Discussionmentioning

confidence: 99%

Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor‐β1

Nakatani

Marui

Hitora

et al. 2002

Journal Orthopaedic Research

133

125

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“…Mutations preventing TGF-β function are also causal for hereditary hemorrhagic telangiectasia, 10 and corneal dystrophy. 11 Over activity of TGF-β leads to Camurati-Engelmann Disease of bone, 12 glomerulonephritis, 13 scar formation, 14 keloids, 15 pulmonary fibrosis, 16 and liver cirrhosis. 17 The TGF-β proteins are synthesized as pre-pro-peptides which are secreted from cells in a primarily inactive form called latent TGF-β 18 consisting of a 25 kD mature region surrounded by the pro region, which is also called the latency associated peptide (figure 1).…”

Section: Tgf-β Synthesismentioning

confidence: 99%

Medical Applications of Transforming Growth Factor-

Flanders¹,

Burmester²

2003

Clinical Medicine & Research

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Transforming growth factor-β (TGF-β) proteins and their antagonists have entered clinical trials. These multi-functional regulators of cell growth and differentiation induce extracellular matrix proteins and suppress the immune system making TGF-βs useful in treatment of wounds with impaired healing, mucositis, fractures, ischemia-reperfusion injuries, and autoimmune disease. In diseases such as keloids, glomerulonephritis and pulmonary fibrosis, excessive expression of TGF-β has been implicated as being responsible for accumulation of detrimental scar tissue. In these conditions, agents that block TGF-β have prevented or reversed disease. Similarly, in carcinogenesis, blocking TGF-β activity may be valuable in stimulating an immune response towards metastasis. As these blocking agents receive approval, we will likely have new therapies for previously recalcitrant diseases.

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“…At the cellular level, increased levels of cytokines and growth factors, or their receptors, and sensitization of mitogenic response to these secreted factors after wounding in KFs have been suggested to play a role in keloid pathogenesis (Calderon et al, 1996). Transforming growth factor (TGF)-b1 and TGF-b2 were found to be elevated in KFs (Lee et al, 1999), and increased sensitivity to TGF-b1 in KFs increased fibronectin (Babu et al, 1992) and collagen production, and cell proliferation (Younai et al, 1994). Platelet-derived growth factor (PDGF)a receptor expression was shown to be enhanced in KFs, which corresponded to increased mitotic response upon exposure to all three PDGF isoforms (Haisa et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Stat3 contributes to keloid pathogenesis via promoting collagen production, cell proliferation and migration

et al. 2006

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Keloids, partially considered as benign tumors, represent the most extreme example of cutaneous scarring that uniquely afflicts humans as a pathological response to wound healing. It is characterized by excessive deposition of collagen and other extracellular matrix components by dermal fibroblasts. Upon cutaneous injury, cocktails of chemokines, cytokines and growth factors are secreted temporally and spatially to direct appropriate responses from neutrophils, macrophages, keratinocytes and fibroblasts to facilitate normal wound healing. Signal transducer and activator of transcription 3 (Stat3) is an oncogene and a latent transcription factor activated by various cytokines and growth factors. We investigated the possible role of Stat3 in keloid scar pathogenesis by examining skin tissue and cultured fibroblasts from keloid-scarred patients. We observed enhanced expression and phosphorylation of Stat3 in keloid scar tissue, and in cultured keloid fibroblasts (KFs) in vitro. Increased activation of Janus kinase (Jak)2, but not Jak1, was detected in KFs, and suppression of Jak2 by its inhibitor repressed Stat3 Y705 phosphorylation. Inhibition of Stat3 expression and phosphorylation by short interfering RNA or Cucurbitacin I resulted in the loss of collagen production, impaired proliferation and delayed cell migration in KFs. We show, for the first time, a role of Stat3 in keloid pathogenesis. Inhibitors of Stat3 may be useful therapeutic strategies for the prospective treatment of keloid scars.

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Expression of Transforming Growth Factor Beta 1, 2, and 3 Proteins in Keloids

Cited by 165 publications

References 0 publications

Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor‐β1

Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor‐β1

Medical Applications of Transforming Growth Factor-

Stat3 contributes to keloid pathogenesis via promoting collagen production, cell proliferation and migration

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