The molecular basis of glucocorticoid-induced skin atrophy: topical glucocorticoid apparently decreases both collagen synthesis and the corresponding collagen mRNA level in human skin in vivo.
The effects of topical betamethasone-17-valerate on collagen propeptide levels, collagen mRNA level, lysyl oxidase mRNA and matrix metalloproteinase (MMP)-1 and MMP-2 mRNA levels were studied in human skin. Three days' treatment of healthy skin with topical betamethasone caused a 70-80% decrease in type I and III collagen propeptides in suction blister fluid. A similar decrease was found in type I collagen mRNA when assayed by either slot-blot hybridization or a quantitative polymerase chain reaction method, indicating that the decrease in collagen synthesis after topical glucocorticoid treatment is apparently due to a decrease in corresponding mRNA. mRNA of lysyl oxidase, which is an important enzyme catalysing the cross-linking of collagen chains, and collagen-degrading enzyme MMP-1 and MMP-2 mRNAs were not decreased in the same skin samples. This suggests that in vivo, glucocorticoids modulate variably the genes involved in collagen synthesis and degradation. Our study provides a solid molecular basis for glucocorticoid-induced dermal atrophy, which results from the decrease in functional collagen mRNA in the skin.
Oikarinen
A
A
Department of Dermatology, Oulu University Hospital, Finland. aarne.oikarinen@oulu.fi
Haapasaari
K M
KM
Sutinen
M
M
Tasanen
K
K
D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001284:Atrophy; D001624:Betamethasone Valerate / Q000009:adverse effects*; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects*; D017364:Collagenases / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D005938:Glucocorticoids; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012867:Skin / Q000473:pathology*