Pretreatment with topical all-trans-retinoic acid is beneficial for wound healing in genetically diabetic mice.
OBJECTIVE
Topical pretreatment with aIl-trans-retinoic acid (atRA) is known to improve healing of cutaneous wounds. We tested the effect of atRA on wound healing of genetically diabetic db/db mice. It is known that cutaneous wounds of db/db mice show delayed wound healing due to impaired wound contraction, delayed granulation tissue formation and underexpression of keratinocyte growth factor (KGF).


METHODS
0.1% atRA in 100 mg aqueous gel was applied to the back skin of db/db mice as well as to their normal heterozygous littermates, db/+ mice, for five consecutive days, and 2 days after completion of the atRA treatment, two round excisional wounds were created down the panniculus carnosus with a 6-mm punch biopsy on the back skin of each mouse.


RESULTS
After 5 days treatment with 0.1% atRA, significant hypertrophy of the epidermis and dermis, neovascularization, and inflammatory cell invasion were seen in the skin of the db/db mice, but these effects were seen only weakly in db/+ mice. Wounds in atRA-treated db/db mice closed more rapidly than those in vehicle-treated db/db mice. KGF mRNA expression, which is usually significantly lower in db/db mice than in normal mice, in wounds of atRA-treated db/db mice on day 1 of treatment was as strong as in db/+ mice.


CONCLUSIONS
Pretreatment with atRA reversed the impaired wound healing in db/db mice.
Kitano
Y
Y
Department Plastic and Reconstructive Surgery, School of Medicine, University of Tokyo. kitano-pla@h.u-tokyo.ac.jp
Yoshimura
K
K
Uchida
G
G
Sato
K
K
Harii
K
K
D000287:Administration, Topical; D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000235:genetics; D007641:Keratolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage* / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*; D014950:Wounds, Penetrating / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*
C496454:Fgf7 protein, mouse; D007641:Keratolytic Agents; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D014212:Tretinoin; D005346:Fibroblast Growth Factors