The Effect of TGF-β on Keloid Fibroblast Proliferation and Collagen Synthesis

Abstract

Keloids are characterized by an overabundant deposition of collagen, and they recur frequently following excision. Fibroblasts isolated from keloid tissue and maintained in cell culture continue to express an increased capacity to produce collagen. In an effort to define the mechanisms responsible for keloid formation, the potential of exogenous transforming growth factor beta 1 (TGF-beta 1) to differentially affect DNA synthesis and collagen expression in cultured human fibroblasts derived from keloid or normal dermis was investigated. In this study, TGF-beta 1 at a concentration of 5.0 ng/ml was found to stimulate DNA synthesis of keloid-derived fibroblasts to a greater extent than fibroblasts derived from normal dermis. With a microassay to measure levels of collagenase-digestible radiolabeled proteins, TGF-beta 1 was found to elicit a greater increase in absolute collagen synthesis in keloid-derived fibroblasts compared with fibroblasts derived from normal dermis. Examination of tRNA(pro) pool-specific activities indicated that these observed differences in rates of collagen synthesis were not the result of unequal rates of proline transport or pool size. Likewise, TGF-beta 1 did not alter the uptake of vitamin C, an essential cofactor and mediator needed for maximal collagen expression. The increase in collagen synthesis by keloid-derived fibroblasts treated with TGF-beta 1 was accompanied by a corresponding increase in procollagen type I mRNA levels, indicating that the differential response of keloid and normal dermal fibroblasts to this growth factor is occurring primarily at a pretranslational level. These results suggest a unique sensitivity of keloid fibroblasts to TGF-beta 1 and thus a possible role for this mediator in keloid pathogenesis.

Effect of the abrogation of TGF-β1 by antisense oligonucleotides on the expression of TGF-β-isoforms and their receptors I and II in isolated fibroblasts from keloid scars

“…Bettinger et al also found a significant increase in the response rate to TGF-ß in KFs, with an increase in fibroblast proliferation and collagen synthesis (15). Increased rates of proliferation and collagen synthesis suggest an altered response of KFs to this cytokine, which might reflect a modification in the regulatory pathway that occurs at the receptor level or during intracellular transduction (4,9).…”

“…Treatment with TGF-ß1 results in an increase in fibronectin biosynthesis leading to an overproduction of ECM components in keloid fibroblasts (3,9). In addition, TGF-ß1 treatment upregulates collagen production, and keloid fibroblasts show a greater proliferative capacity than normal human dermal fibroblasts (3,15,16).…”

Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

“…[5][6][7][8][9][10][11][12] Modifications in growth factor-regulated cell growth and apoptosis, intracellular signal transduction, and epidermis-dermis interactions have been reported. [13][14][15][16][17][18][19][20][21] Changes in the level of genes involved in the above phenomena were also detected in gene profiling studies. 22,23 Despite these findings, knowledge-based specific approaches for prevention and efficacious treatment of keloids are still absent, and the lack of proper in vitro and animal models that recapitulate the pathophysiology of keloids further hampers progress.…”

Peak Plasma Blade and Coblation Adenotonsillectomy: Report Of 2 Cases and Literature Review

“…As for PEAK PlasmaBlade versus conventional surgery, one study showed significant reduction in thermal injury and improved wound strength and histology with better visual assesment of scars 6 . It has been shown that PEAK PlasmaBlade reduces level of inflammation, thus leading to good epithelization resulting in improved healing and cosmesis [10][11][12] .…”