Gene expression in normal and doxorubicin-impaired wounds: importance of transforming growth factor-beta.
The function of transforming growth factor-beta (TGF-beta) in vivo remains unknown despite the fact that it has been identified in numerous biologic processes involving the regulation of cell growth including tissue repair. Doxorubicin is a potent antitumor drug that has been shown to have detrimental effects on wound healing. With specific complementary DNA probes for TFG-beta and type 1 collagen, RNA from wounds of rats treated with saline solution and doxorubicin was analyzed for the expression of each gene at different times after wounding. In a second study, either 2 micrograms exogenous TGF-beta or vehicle was added to wounds of rats treated with doxorubicin, and wound RNA was analyzed in a similar manner. In wounds from rats treated with saline solution, messenger RNA (mRNA) for TGF-beta peaks on day 7 after wounding and is also elevated on days 3 and 10; mRNA for collagen is elevated on days 7 and 10. Doxorubicin decreases mRNA for TGF-beta and collagen on each day. Topical application of TGF-beta to wounds of rats treated with doxorubicin increases collagen mRNA levels to normal or supranormal levels. This study suggests that the impaired healing induced by doxorubicin may be a result of decreased gene expression for TGF-beta and that topical replacement of this growth factor may correct the defect.
Salomon
G D
GD
Surgery Branch, National Cancer Institute/NIH, Bethesda, MD 20892.
Kasid
A
A
Bernstein
E
E
Buresh
C
C
Director
E
E
Norton
J A
JA
D000818:Animals; D003094:Collagen / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D015291:Transforming Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014947:Wounds and Injuries / Q000235:genetics*
D012333:RNA, Messenger; D015291:Transforming Growth Factors; D004317:Doxorubicin; D003094:Collagen