The effect of decorinas an antagonist of tgf-betain fetal rat wound healing

Shin, Keuk Shun; Yoo, Won Min; Kwark, Hyug Jun

Abstract

Adult wounds heal with scar-tissue formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. The unique fetal wound repair process is not dependent on the sterile, aqueous intrauterine environment. The differences between fetal and adult wound healing appear to reflect processes intrinsic to fetal tissue, such as the unique fetal fibroblast, a more rapid and ordered deposition and turnover of tissue components, and, particularly, a markedly reduced inflammatory infiltrate and cytokine profile. Among these cytokines, the transforming growth factor-beta(TGF-beta) is a growth factor which plays an important role in the regulation of cell growth and differentiation. The fibrosis characteristic of adult wound repair may be associated with TGF-betaexcess. Recent experimental studies have focused on the specific anti-TGF-beta strategies for scarless wound healing. Decorin, a proteoglycan, is known to regulate TGF-beta. This factor antagonizes the action of TGF-betain tissues. However, little is known about the functions of this factor in vivo. The objects of the present study were to analyze the effects of TGF-beta, an important regulatory molecule in adult healing events, and the effects of decorin, known inhibitor against TGF-beta, on the fetal tissue response following wounding. Fetal cellular and extracellular matrix response to injury were evaluated by treating the wound with TGF-beta and decorin in fetal rat at 14 days gestation (term = 21 days). Histologic response and histomorphometric analysis two to eight weeks later were compared between TGF-betaonly treated wound and TGF-betawith decorin treated wound.The histologic finding of the TGF-beta treated wound was characterized by an early acute inflammatory response : by week 6 fibroblasts and collagen were predominant. In contrast, TGF-beta with decorin treated wound had no remarkable histologic evidence of acute inflammation or fibroblast penetration and few collagen was deposited. These observations demonstrate that the fetal response becomes adultlike with fibroblast proliferation and collagen accumulation when TGF-betais added, thus documenting the responsiveness of the fetal system to adult repair signals. Such responsiveness thus suggests a critical difference in the fetal wound environment. Fetal repair may proceed in the absence of trophic factors like TGF-beta, thus accounting for optimal "healing" in the absence of excessive fibrosis. And these observations also confirmed the inhibitory action of decorin against TGF-beta in rat fetus model. We can suggest that the decorin minimize the inflammatory response and subsequent cellular proliferation in wound healing process, thus eventually prevent collagen deposition and scar tissue formation.

The effect of decorinas an antagonist of tgf-betain fetal rat wound healing

Abstract

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