Abstract:

Recombinant human transforming growth factor(TGF)β3 is an important cytokine for formation of healthy skin and healing response of embryos without scarring. In actively growing hypertrophic scar fibroblasts, the expression of TGFβ2 increases and TGFβ3 is low. However, in embryonic scar-free healing, TGFβ3 is high. When TGFβ1, TGFβ2, and TGFβ3 combine with the same receptor complex on the cell surface, TGFβ3 induces the receptor to compete with TGFβ1 and TGFβ2 to reduce their expression and inhibit the formation of scars. In the late period of wound healing, TGFβ3 reduces scar size to reverse the effects of TGFβ1 and TGFβ2 by decreasing the aggregates of inflammatory cells and the deposition of connective tissue, ensuring wound healing and preventing excessive scarring. Preclinical safety and toxicology studies suggest that the TGF β family of proteins accumulate mainly in the liver(~60%) and in other tissues, including the kidneys(~20%) and the blood(~10%). In addition, the TGFβ family of proteins minimally(<10%) accumulates in the lungs, spleen, adrenals, stomach, small intestine, cardiac and skeletal muscles, and cerebral cortex. Safety pharmacology studies investigating i.v. dosing of recombinant human TGFβ3 in rats and dogs have demonstrated the absence of adverse effects on major systems, including the central nervous system and respiratory or cardiovascular functions at doses up to and including 3 μg·kg-1 following prolonged(daily for 3 months) administration. Recombinant human TGFβ3 was injected into the skin in the cut edge of adult rats to reduce distinct scars and to improve skin construct.

Key words: transforming growth factor, scar, formation, prevention