Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy?
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...
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doaj-e66b335a3a114bbbad4e9845467038e42020-11-25T01:09:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8946710.1371/journal.pone.0089467Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy?Jung-Yi Lisa ChanKuo-Hsien WangChia-Lang FangWei-Yu ChenFibrous 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.http://europepmc.org/articles/PMC3928451?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jung-Yi Lisa Chan Kuo-Hsien Wang Chia-Lang Fang Wei-Yu Chen |
spellingShingle |
Jung-Yi Lisa Chan Kuo-Hsien Wang Chia-Lang Fang Wei-Yu Chen Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy? PLoS ONE |
author_facet |
Jung-Yi Lisa Chan Kuo-Hsien Wang Chia-Lang Fang Wei-Yu Chen |
author_sort |
Jung-Yi Lisa Chan |
title |
Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy? |
title_short |
Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy? |
title_full |
Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy? |
title_fullStr |
Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy? |
title_full_unstemmed |
Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy? |
title_sort |
fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy? |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3928451?pdf=render |
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