Angiopoietin-like 4 regulates epidermal differentiation.

The nuclear hormone receptor PPARβ/δ is integral to efficient wound re-epithelialization and implicated in epidermal maturation. However, the mechanism underlying the latter process of epidermal differentiation remains unclear. We showed that ligand-activated PPARβ/δ indirectly stimulated keratinocy...

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Autores principales:	Mintu Pal, Ming Jie Tan, Royston-Luke Huang, Yan Yih Goh, Xiao Ling Wang, Mark Boon Yang Tang, Nguan Soon Tan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df5e674e0bc04de691982aed18aef7ab
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spelling	oai:doaj.org-article:df5e674e0bc04de691982aed18aef7ab2021-11-04T06:07:57ZAngiopoietin-like 4 regulates epidermal differentiation.1932-620310.1371/journal.pone.0025377https://doaj.org/article/df5e674e0bc04de691982aed18aef7ab2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21966511/?tool=EBIhttps://doaj.org/toc/1932-6203The nuclear hormone receptor PPARβ/δ is integral to efficient wound re-epithelialization and implicated in epidermal maturation. However, the mechanism underlying the latter process of epidermal differentiation remains unclear. We showed that ligand-activated PPARβ/δ indirectly stimulated keratinocyte differentiation, requiring de novo gene transcription and protein translation. Using organotypic skin cultures constructed from PPARβ/δ- and angiopoietin-like 4 (ANGPTL4)-knockdown human keratinocytes, we showed that the expression of ANGPTL4, a PPARβ/δ target gene, is essential for the receptor mediated epidermal differentiation. The pro-differentiation effect of PPARβ/δ agonist GW501516 was also abolished when keratinocytes were co-treated with PPARβ/δ antagonist GSK0660 and similarly in organotypic skin culture incubated with blocking ANGPTL4 monoclonal antibody targeted against the C-terminal fibrinogen-like domain. Our focused real-time PCR gene expression analysis comparing the skin biopsies from wildtype and ANGPTL4-knockout mice confirmed a consistent down-regulation of numerous genes involved in epidermal differentiation and proliferation in the ANGPTL4-knockout skin. We further showed that the deficiency of ANGPTL4 in human keratinocytes and mice skin have diminished expression of various protein kinase C isotypes and phosphorylated transcriptional factor activator protein-1, which are well-established for their roles in keratinocyte differentiation. Chromatin immunoprecipitation confirmed that ANGPTL4 stimulated the activation and binding of JUNB and c-JUN to the promoter region of human involucrin and transglutaminase type 1 genes, respectively. Taken together, we showed that PPARβ/δ regulates epidermal maturation via ANGPTL4-mediated signalling pathway.Mintu PalMing Jie TanRoyston-Luke HuangYan Yih GohXiao Ling WangMark Boon Yang TangNguan Soon TanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e25377 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mintu Pal Ming Jie Tan Royston-Luke Huang Yan Yih Goh Xiao Ling Wang Mark Boon Yang Tang Nguan Soon Tan Angiopoietin-like 4 regulates epidermal differentiation.
description	The nuclear hormone receptor PPARβ/δ is integral to efficient wound re-epithelialization and implicated in epidermal maturation. However, the mechanism underlying the latter process of epidermal differentiation remains unclear. We showed that ligand-activated PPARβ/δ indirectly stimulated keratinocyte differentiation, requiring de novo gene transcription and protein translation. Using organotypic skin cultures constructed from PPARβ/δ- and angiopoietin-like 4 (ANGPTL4)-knockdown human keratinocytes, we showed that the expression of ANGPTL4, a PPARβ/δ target gene, is essential for the receptor mediated epidermal differentiation. The pro-differentiation effect of PPARβ/δ agonist GW501516 was also abolished when keratinocytes were co-treated with PPARβ/δ antagonist GSK0660 and similarly in organotypic skin culture incubated with blocking ANGPTL4 monoclonal antibody targeted against the C-terminal fibrinogen-like domain. Our focused real-time PCR gene expression analysis comparing the skin biopsies from wildtype and ANGPTL4-knockout mice confirmed a consistent down-regulation of numerous genes involved in epidermal differentiation and proliferation in the ANGPTL4-knockout skin. We further showed that the deficiency of ANGPTL4 in human keratinocytes and mice skin have diminished expression of various protein kinase C isotypes and phosphorylated transcriptional factor activator protein-1, which are well-established for their roles in keratinocyte differentiation. Chromatin immunoprecipitation confirmed that ANGPTL4 stimulated the activation and binding of JUNB and c-JUN to the promoter region of human involucrin and transglutaminase type 1 genes, respectively. Taken together, we showed that PPARβ/δ regulates epidermal maturation via ANGPTL4-mediated signalling pathway.
format	article
author	Mintu Pal Ming Jie Tan Royston-Luke Huang Yan Yih Goh Xiao Ling Wang Mark Boon Yang Tang Nguan Soon Tan
author_facet	Mintu Pal Ming Jie Tan Royston-Luke Huang Yan Yih Goh Xiao Ling Wang Mark Boon Yang Tang Nguan Soon Tan
author_sort	Mintu Pal
title	Angiopoietin-like 4 regulates epidermal differentiation.
title_short	Angiopoietin-like 4 regulates epidermal differentiation.
title_full	Angiopoietin-like 4 regulates epidermal differentiation.
title_fullStr	Angiopoietin-like 4 regulates epidermal differentiation.
title_full_unstemmed	Angiopoietin-like 4 regulates epidermal differentiation.
title_sort	angiopoietin-like 4 regulates epidermal differentiation.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/df5e674e0bc04de691982aed18aef7ab
work_keys_str_mv	AT mintupal angiopoietinlike4regulatesepidermaldifferentiation AT mingjietan angiopoietinlike4regulatesepidermaldifferentiation AT roystonlukehuang angiopoietinlike4regulatesepidermaldifferentiation AT yanyihgoh angiopoietinlike4regulatesepidermaldifferentiation AT xiaolingwang angiopoietinlike4regulatesepidermaldifferentiation AT markboonyangtang angiopoietinlike4regulatesepidermaldifferentiation AT nguansoontan angiopoietinlike4regulatesepidermaldifferentiation
_version_	1718445181894656000

Angiopoietin-like 4 regulates epidermal differentiation.

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