Transforming growth factors beta1, beta2, and beta3 and their receptors are differentially regulated during normal and impaired wound healing.
A series of studies has shown that application of transforming growth factor beta (TGF-beta) to a wound has a beneficial effect, especially in animals with wound healing disorders. In this study we have investigated the regulation of TGF-beta1, beta2, and beta3 and their receptors during the repair process. We found a large induction of all three TGF-beta isoforms and also of TGF-beta types I and II receptors, although the time course of induction and the absolute expression levels were different for these genes. Furthermore, each TGF-beta isoform had distinct sites of expression in the wound. Systemic treatment with glucocorticoids significantly altered the expression levels of TGF-betas and TGF-beta receptors. Whereas expression of TGF-beta1, TGF-beta2, and TGF-beta type II receptor was suppressed by glucocorticoids in normal and wounded skin, expression of TGF-beta3 and TGF-beta receptor type I mRNA was stimulated. These findings provide an explanation for the beneficial effect of exogenous TGF-beta in the treatment of impaired wound healing in glucocorticoid-treated animals. Furthermore, they suggest that a disturbed balance between the levels of the three TGF- beta isoforms and their receptors might underlie the wound healing defect seen in glucocorticoid-treated animals.
Frank
S
S
Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
Madlener
M
M
Werner
S
S
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D004817:Epidermis / Q000502:physiology; D005260:Female; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology*; D012879:Skin Physiological Phenomena; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014945:Wound Healing
D017931:DNA Primers; D005938:Glucocorticoids; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003907:Dexamethasone