Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.

<h4>Background</h4>Cathepsin K (CatK), a cysteine protease with the potent elastolytic activity, plays a predominant role in intracellular elastin degradation in human dermal fibroblasts (HDFs), and contributes to solar elastosis. In previous studies, CatK expression was downregulated in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Qingfang Xu, Wei Hou, Yue Zheng, Chen Liu, Zijian Gong, Chun Lu, Wei Lai, Howard I Maibach
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b44c3290fc44d4a89b06962405e96c5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5b44c3290fc44d4a89b06962405e96c5
record_format	dspace
spelling	oai:doaj.org-article:5b44c3290fc44d4a89b06962405e96c52021-11-25T06:07:43ZUltraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.1932-620310.1371/journal.pone.0102732https://doaj.org/article/5b44c3290fc44d4a89b06962405e96c52014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25048708/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Cathepsin K (CatK), a cysteine protease with the potent elastolytic activity, plays a predominant role in intracellular elastin degradation in human dermal fibroblasts (HDFs), and contributes to solar elastosis. In previous studies, CatK expression was downregulated in photoaged skin and fibroblasts, but upregulated in acute UVA-irradiated skin and fibroblasts. The underlying mechanisms regulating UVA-induced CatK expression remain elusive.<h4>Objective</h4>This study investigates mechanisms involved in the regulation of UVA-induced CatK expression in HDFs.<h4>Methods</h4>Primary HDFs were exposed to UVA. Cell proliferation was analyzed using a colorimetric assay of relative cell number. Quantitative real-time RT-PCR and Western blot were performed to detect CatK expression in HDFs on three consecutive days after 10 J/cm2 UVA irradiation, or cells treated with increasing UVA doses. UVA-activated MAPK/AP-1 pathway was examined by Western blot. Effects of inhibition of MAPK pathway and knockdown of Jun and Fos on UVA-induced CatK expression were also measured by real-time RT-PCR and Western blot.<h4>Results</h4>UVA significantly increased CatK mRNA and protein expression in a dose-dependent manner. UVA-induced CatK expression occurred along with UVA-activated phosphorylation of JNK, p38 and Jun, UVA-increased expression of Fos. Inactivation of JNK and p38MAPK pathways both remarkably decreased UVA-induced CatK expression, which was suppressed more by inhibition of JNK pathway. Furthermore, knockdown of Jun and Fos significantly attenuated basal and UVA-induced CatK expression.<h4>Conclusion</h4>UVA is capable of increasing CatK expression in HDFs, most likely by activation of MAPK pathway and of AP-1, which has been shown to be the case for matrix metalloproteinases. As current strategies for selecting anti-photoaging agents focus on their ability to decrease MMPs' expression through inhibiting UV- activated MAPK pathway, future strategies should also consider their effect on CatK expression.Qingfang XuWei HouYue ZhengChen LiuZijian GongChun LuWei LaiHoward I MaibachPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e102732 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qingfang Xu Wei Hou Yue Zheng Chen Liu Zijian Gong Chun Lu Wei Lai Howard I Maibach Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.
description	<h4>Background</h4>Cathepsin K (CatK), a cysteine protease with the potent elastolytic activity, plays a predominant role in intracellular elastin degradation in human dermal fibroblasts (HDFs), and contributes to solar elastosis. In previous studies, CatK expression was downregulated in photoaged skin and fibroblasts, but upregulated in acute UVA-irradiated skin and fibroblasts. The underlying mechanisms regulating UVA-induced CatK expression remain elusive.<h4>Objective</h4>This study investigates mechanisms involved in the regulation of UVA-induced CatK expression in HDFs.<h4>Methods</h4>Primary HDFs were exposed to UVA. Cell proliferation was analyzed using a colorimetric assay of relative cell number. Quantitative real-time RT-PCR and Western blot were performed to detect CatK expression in HDFs on three consecutive days after 10 J/cm2 UVA irradiation, or cells treated with increasing UVA doses. UVA-activated MAPK/AP-1 pathway was examined by Western blot. Effects of inhibition of MAPK pathway and knockdown of Jun and Fos on UVA-induced CatK expression were also measured by real-time RT-PCR and Western blot.<h4>Results</h4>UVA significantly increased CatK mRNA and protein expression in a dose-dependent manner. UVA-induced CatK expression occurred along with UVA-activated phosphorylation of JNK, p38 and Jun, UVA-increased expression of Fos. Inactivation of JNK and p38MAPK pathways both remarkably decreased UVA-induced CatK expression, which was suppressed more by inhibition of JNK pathway. Furthermore, knockdown of Jun and Fos significantly attenuated basal and UVA-induced CatK expression.<h4>Conclusion</h4>UVA is capable of increasing CatK expression in HDFs, most likely by activation of MAPK pathway and of AP-1, which has been shown to be the case for matrix metalloproteinases. As current strategies for selecting anti-photoaging agents focus on their ability to decrease MMPs' expression through inhibiting UV- activated MAPK pathway, future strategies should also consider their effect on CatK expression.
format	article
author	Qingfang Xu Wei Hou Yue Zheng Chen Liu Zijian Gong Chun Lu Wei Lai Howard I Maibach
author_facet	Qingfang Xu Wei Hou Yue Zheng Chen Liu Zijian Gong Chun Lu Wei Lai Howard I Maibach
author_sort	Qingfang Xu
title	Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.
title_short	Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.
title_full	Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.
title_fullStr	Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.
title_full_unstemmed	Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.
title_sort	ultraviolet a-induced cathepsin k expression is mediated via mapk/ap-1 pathway in human dermal fibroblasts.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/5b44c3290fc44d4a89b06962405e96c5
work_keys_str_mv	AT qingfangxu ultravioletainducedcathepsinkexpressionismediatedviamapkap1pathwayinhumandermalfibroblasts AT weihou ultravioletainducedcathepsinkexpressionismediatedviamapkap1pathwayinhumandermalfibroblasts AT yuezheng ultravioletainducedcathepsinkexpressionismediatedviamapkap1pathwayinhumandermalfibroblasts AT chenliu ultravioletainducedcathepsinkexpressionismediatedviamapkap1pathwayinhumandermalfibroblasts AT zijiangong ultravioletainducedcathepsinkexpressionismediatedviamapkap1pathwayinhumandermalfibroblasts AT chunlu ultravioletainducedcathepsinkexpressionismediatedviamapkap1pathwayinhumandermalfibroblasts AT weilai ultravioletainducedcathepsinkexpressionismediatedviamapkap1pathwayinhumandermalfibroblasts AT howardimaibach ultravioletainducedcathepsinkexpressionismediatedviamapkap1pathwayinhumandermalfibroblasts
_version_	1718414164293058560

Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.

Ejemplares similares