Aldosterone and mineralocorticoid receptor antagonists modulate elastin and collagen deposition in human skin.
We have shown that the steroid hormone aldosterone, recognized for its action on the kidney and the cardiovascular system, also modulates deposition of extracellular matrix in human skin. We have shown that treatment of primary cultures of normal skin fibroblasts with aldosterone (10 n-1 μM), in addition to stimulation of collagen type I expression, induces elastin gene expression and elastic fiber deposition. We have further shown that the elastogenic effect of aldosterone, which can be enhanced in the presence of mineralocorticoid receptor (MR) antagonists spironolactone and eplerenone, is executed in a MR-independent manner via amplification of IGF-I receptor-mediated signaling. Because aldosterone applied alone stimulates both collagen and elastin deposition in cultures of fibroblasts and in cultures of skin explants derived from dermal stretch marks, we postulate that this steroid should be used in the treatment of damaged skin that loses its volume and elasticity. Moreover, aldosterone applied in conjunction with spironolactone or eplerenone induces matrix remodeling and exclusively enhances elastogenesis in cultures of fibroblasts and explants derived from dermal scars and keloids. We therefore propose that intra-lesional injection of these factors should be considered in therapy for disfiguring dermal lesions and especially in prevention of their recurrence after surgical excision.
Hospital for Sick Children, Toronto, Canada.
Thomas F
TF
Mitts
Severa
S
Bunda
Yanting
Y
Wang
Aleksander
A
Hinek
D000328:Adult; D000450:Aldosterone / Q000494:pharmacology; D001706:Biopsy; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D004548:Elasticity; D004549:Elastin / Q000235:genetics / Q000378:metabolism*; D000077545:Eplerenone; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007627:Keloid / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D024042:Collagen Type I; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D004549:Elastin; D017526:Receptor, IGF Type 1