In vivo prevention of corticosteroid-induced skin atrophy by tretinoin in the hairless mouse is accompanied by modulation of collagen, glycosaminoglycans, and fibronectin.
In an earlier study we showed that tretinoin could prevent corticosteroid-induced skin atrophy in hairless mice. In this study, we examined the histochemical, biochemical, and immunochemical changes that accompanied the atrophy and its prevention. Mice were treated dorsally for 3 weeks in the morning and afternoon (AM:PM) as follows: 1) vehicle:vehicle, 2) steroid:vehicle, 3) steroid:tretinoin. Tretinoin concentration was 0.05% in an ethanol:propylene glycol vehicle. The steroid was clobetasol propionate (0.05%). The normally sparse dermal glycosaminoglycans were further reduced by steroid:vehicle treatment and increased to greater than vehicle:vehicle amounts by steroid:retinoid. Mast cells were similarly affected. Biochemical quantification of glycosaminoglycans confirmed the histochemical findings. Collagen, non-collagenous protein, and total protein content were reduced by the steroid. The latter two were returned to more normal levels by tretinoin whereas with collagen there was only a trend toward normal levels. Fibronectin, which was increased by the steroid:vehicle treatment, was reduced to more normal levels by steroid:tretinoin. We conclude that tretinoin has the ability to prevent the major steroid-induced biomechanical changes in hairless mouse dermal connective tissue that contribute to atrophy.
Schwartz
E
E
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104-6142.
Mezick
J A
JA
Gendimenico
G J
GJ
Kligman
L H
LH
D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000517:prevention & control; D002990:Clobetasol / Q000009:adverse effects / Q000031:analogs & derivatives; D003094:Collagen / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000032:analysis / Q000378:metabolism*; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007501:Iron; D008407:Mast Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008812:Mice, Hairless; D012176:Retinoids / Q000494:pharmacology; D012867:Skin / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D014048:Tolonium Chloride; D014212:Tretinoin / Q000494:pharmacology*
D000305:Adrenal Cortex Hormones; D005353:Fibronectins; D006025:Glycosaminoglycans; D012176:Retinoids; D014048:Tolonium Chloride; D014212:Tretinoin; D003094:Collagen; D002990:Clobetasol; D007501:Iron