[HTML][HTML] Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway …

JYL Chan, KH Wang, CL Fang, WY Chen - PLoS One, 2014 - journals.plos.org
JYL Chan, KH Wang, CL Fang, WY Chen
PLoS One, 2014journals.plos.org
Fibrous papules of the face are hamartomas characterized by stellate-shaped stromal cells,
multinucleated giant cells, and proliferative blood vessels in the dermis. The pathogenesis of
fibrous papules remains unclear. There is a striking microscopic resemblance between
fibrous papules and tuberous sclerosis complex (TSC)-associated angiofibromas. A
germline mutation of the TSC1 or TSC2 gene, leading to activation of the mammalian target
of rapamycin (mTOR) pathway, accounts for the pathogenesis of TSC-associated …
Fibrous papules of the face are hamartomas characterized by stellate-shaped stromal cells, multinucleated giant cells, and proliferative blood vessels in the dermis. The pathogenesis of fibrous papules remains unclear. There is a striking microscopic resemblance between fibrous papules and tuberous sclerosis complex (TSC)-associated angiofibromas. A germline mutation of the TSC1 or TSC2 gene, leading to activation of the mammalian target of rapamycin (mTOR) pathway, accounts for the pathogenesis of TSC-associated angiofibromas. Activated mTOR subsequently activates p70 ribosomal protein S6 kinase (p70S6K) and ribosomal protein S6 (S6) by phosphorylation. Rapamycin, a mTOR inhibitor, is effective in treating TSC-associated angiofibromas. The aim of this study was to understand whether the mTOR pathway is activated in fibrous papules. We studied immunoexpressions of phosphorylated (p-) mTOR effectors in fibrous papules, TSC-associated angiofibromas, and normal skin controls. P-mTOR, p-p70S6K and p-S6 were highly expressed in dermal stromal cells and epidermal keratinocytes in fibrous papules and TSC-associated angiofibromas but not in fibroblasts and epidermal keratinocytes of normal skin controls (p<0.001). The results suggest topical rapamycin may be a novel treatment option for fibrous papules.
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