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11β-Hydroxysteroid Dehydrogenase 1 Specific Inhibitor Increased Dermal Collagen Content and Promotes Fibroblast Proliferation

Glucocorticoids (GCs) are one of the most effective anti-inflammatory drugs for treating acute and chronic inflammatory diseases. However, several studies have shown that GCs alter collagen metabolism in the skin and induce skin atrophy. Cortisol is the endogenous GC that is released in response to...

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Autores principales: Terao, Mika, Tani, Mamori, Itoi, Saori, Yoshimura, Takuji, Hamasaki, Toshimitsu, Murota, Hiroyuki, Katayama, Ichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965512/
https://www.ncbi.nlm.nih.gov/pubmed/24667799
http://dx.doi.org/10.1371/journal.pone.0093051
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author Terao, Mika
Tani, Mamori
Itoi, Saori
Yoshimura, Takuji
Hamasaki, Toshimitsu
Murota, Hiroyuki
Katayama, Ichiro
author_facet Terao, Mika
Tani, Mamori
Itoi, Saori
Yoshimura, Takuji
Hamasaki, Toshimitsu
Murota, Hiroyuki
Katayama, Ichiro
author_sort Terao, Mika
collection PubMed
description Glucocorticoids (GCs) are one of the most effective anti-inflammatory drugs for treating acute and chronic inflammatory diseases. However, several studies have shown that GCs alter collagen metabolism in the skin and induce skin atrophy. Cortisol is the endogenous GC that is released in response to various stressors. Over the last decade, extraadrenal cortisol production in various tissues has been reported. Skin also synthesizes cortisol through a de novo pathway and through an activating enzyme. 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is the enzyme that catalyzes the conversion of hormonally inactive cortisone to active cortisol in cells. We previously found that 11β-HSD1 negatively regulates proliferation of keratinocytes. To determine the function of 11β-HSD1 in dermal fibroblasts and collagen metabolism, the effect of a selective 11β-HSD1 inhibitor was studied in mouse tissues and dermal fibroblasts. The expression of 11β-HSD1 increased with age in mouse skin. Subcutaneous injection of a selective 11β-HSD1 inhibitor increased dermal thickness and collagen content in the mouse skin. In vitro, proliferation of dermal fibroblasts derived from 11β-HSD1 null mice (Hsd11b1(−/−) mice) was significantly increased compared with fibroblasts from wild-type mice. However, in vivo, dermal thickness of Hsd11b1(−/−) mice was not altered in 3-month-old and 1-year-old mouse skin compared with wild-type mouse skin. These in vivo findings suggest the presence of compensatory mechanisms in Hsd11b1(−/−) mice. Our findings suggest that 11β-HSD1 inhibition may reverse the decreased collagen content observed in intrinsically and extrinsically aged skin and in skin atrophy that is induced by GC treatment.
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spelling pubmed-39655122014-03-27 11β-Hydroxysteroid Dehydrogenase 1 Specific Inhibitor Increased Dermal Collagen Content and Promotes Fibroblast Proliferation Terao, Mika Tani, Mamori Itoi, Saori Yoshimura, Takuji Hamasaki, Toshimitsu Murota, Hiroyuki Katayama, Ichiro PLoS One Research Article Glucocorticoids (GCs) are one of the most effective anti-inflammatory drugs for treating acute and chronic inflammatory diseases. However, several studies have shown that GCs alter collagen metabolism in the skin and induce skin atrophy. Cortisol is the endogenous GC that is released in response to various stressors. Over the last decade, extraadrenal cortisol production in various tissues has been reported. Skin also synthesizes cortisol through a de novo pathway and through an activating enzyme. 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is the enzyme that catalyzes the conversion of hormonally inactive cortisone to active cortisol in cells. We previously found that 11β-HSD1 negatively regulates proliferation of keratinocytes. To determine the function of 11β-HSD1 in dermal fibroblasts and collagen metabolism, the effect of a selective 11β-HSD1 inhibitor was studied in mouse tissues and dermal fibroblasts. The expression of 11β-HSD1 increased with age in mouse skin. Subcutaneous injection of a selective 11β-HSD1 inhibitor increased dermal thickness and collagen content in the mouse skin. In vitro, proliferation of dermal fibroblasts derived from 11β-HSD1 null mice (Hsd11b1(−/−) mice) was significantly increased compared with fibroblasts from wild-type mice. However, in vivo, dermal thickness of Hsd11b1(−/−) mice was not altered in 3-month-old and 1-year-old mouse skin compared with wild-type mouse skin. These in vivo findings suggest the presence of compensatory mechanisms in Hsd11b1(−/−) mice. Our findings suggest that 11β-HSD1 inhibition may reverse the decreased collagen content observed in intrinsically and extrinsically aged skin and in skin atrophy that is induced by GC treatment. Public Library of Science 2014-03-25 /pmc/articles/PMC3965512/ /pubmed/24667799 http://dx.doi.org/10.1371/journal.pone.0093051 Text en © 2014 Terao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Terao, Mika
Tani, Mamori
Itoi, Saori
Yoshimura, Takuji
Hamasaki, Toshimitsu
Murota, Hiroyuki
Katayama, Ichiro
11β-Hydroxysteroid Dehydrogenase 1 Specific Inhibitor Increased Dermal Collagen Content and Promotes Fibroblast Proliferation
title 11β-Hydroxysteroid Dehydrogenase 1 Specific Inhibitor Increased Dermal Collagen Content and Promotes Fibroblast Proliferation
title_full 11β-Hydroxysteroid Dehydrogenase 1 Specific Inhibitor Increased Dermal Collagen Content and Promotes Fibroblast Proliferation
title_fullStr 11β-Hydroxysteroid Dehydrogenase 1 Specific Inhibitor Increased Dermal Collagen Content and Promotes Fibroblast Proliferation
title_full_unstemmed 11β-Hydroxysteroid Dehydrogenase 1 Specific Inhibitor Increased Dermal Collagen Content and Promotes Fibroblast Proliferation
title_short 11β-Hydroxysteroid Dehydrogenase 1 Specific Inhibitor Increased Dermal Collagen Content and Promotes Fibroblast Proliferation
title_sort 11β-hydroxysteroid dehydrogenase 1 specific inhibitor increased dermal collagen content and promotes fibroblast proliferation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965512/
https://www.ncbi.nlm.nih.gov/pubmed/24667799
http://dx.doi.org/10.1371/journal.pone.0093051
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