Effect of topical recombinant TGF-beta on healing of partial thickness injuries.
Peptide growth factors produced by platelets, macrophages, epidermal, and dermal cells may play key roles in regulating healing of partial-thickness skin wounds. We examined the effects of recombinant transforming growth factor beta (TGF-beta) on cultures of epidermal and dermal cells in vitro and on healing of partial-thickness injuries in vivo. Increasing concentrations of TGF-beta (0.1, 1, and 10 ng/ml) progressively inhibited serum-stimulated DNA synthesis by up to 95% in cultures of adult human keratinocytes during 48 hr of exposure to TGF-beta. In contrast, TGF-beta (10 and 100 ng/ml) in serum-free media stimulated DNA synthesis by up to 80% compared to serum-free control cultures of adult human dermal fibroblasts. To evaluate the effects of TGF-beta on healing of partial-thickness injuries in vivo, wounds (20 x 20 x 0.6 mm) were created on the dorsal thoracolumbar region of adult pigs by an electrokeratome and were treated daily for 5 days after injury with vehicle or vehicle containing 0.1 or 1 microgram/ml TGF-beta and covered with occlusive dressing. Computerized planimetry of wound photographs demonstrated that TGF-beta treatment stimulated statistically significantly increases in the area of regenerated epidermis compared to wounds treated with saline vehicle on Days 3, 4, 5, and 7 after injury probably due to TGF-beta increasing the rate of epidermal cell migration. In addition, morphometry of biopsy specimens showed that TGF-beta treatment stimulated statistically significant increases in the cross-sectional depths of regenerated dermis compared to wounds treated with saline or Silvadene vehicles on Days 5, 6, and 8 after injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Jones
S C
SC
Department of Surgery, University of Louisville, Kentucky 40292.
Curtsinger
L J
LJ
Whalen
J D
JD
Pietsch
J D
JD
Ackerman
D
D
Brown
G L
GL
Schultz
G S
GS
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D011994:Recombinant Proteins; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013552:Swine; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing; D014947:Wounds and Injuries / Q000473:pathology
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D004247:DNA