MODULATION OF COLLAGEN-SYNTHESIS BY TRANSFORMING GROWTH-FACTOR-BETA IN KELOID AND HYPERTROPHIC SCAR FIBROBLASTS

Keloid and hypertrophic scars are fibrous growths characterized by ove rabundant collagen deposition. We examined the effect of transforming growth factor-beta (TGF-beta), a known stimulant for the production of connective tissue matrices, on the rate of collagen synthesis in kelo id fibroblasts (KFs), hypertrophic scar fibroblasts (HSFs), and normal skin fibroblasts (NSFs). Fibroblasts were cultured in three-dimension al fibrin-gel matrices in the presence or absence of TGF-beta (5 ng/ml ) or anti-TGF-beta neutralizing antibody (50 mug/ml). Secreted collage n levels, labeled with H-3-proline, were measured after 48 hours. KFs produced up to 12 times more collagen than NSFs, and up to 4 times mor e than HSFs. Although KFs increased their rate of collagen production by up to 2.7 times in response to TGF-beta, HSFs and NSFs did not (p = 0.065). Anti-TGF-beta antibody reduced the rate of collagen synthesis of KFs by 40% (p = 0.003), although it did not suppress collagen prod uction in HSFs (p = 0.06) and NSFs (p = 0.75). We conclude that althou gh KFs and HSFs are similar in that they both overproduce collagen, th ey are different in that only KFs display a marked sensitivity to TGF- beta, which is abundant during the proliferative phase of wound healin g.