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Angiopoietin-like 4 regulates epidermal differentiation

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Angiopoietin-like 4 regulates epidermal differentiation

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dc.contributor.author Mintu Pal
dc.contributor.author Tan, Ming Jie
dc.contributor.author Huang, Royston-Luke
dc.contributor.author Goh, Yan Yih
dc.contributor.author Wang, Xiao Ling
dc.contributor.author Tang, Mark Boon Yang
dc.contributor.author Tan, Nguan Soon
dc.date.accessioned 2011-10-03T06:41:33Z
dc.date.available 2011-10-03T06:41:33Z
dc.date.copyright 2011
dc.date.issued 2011-10-03
dc.identifier.citation Pal, M., Tan, M. J., Huang, R. L., Goh, Y. Y., Wang, X. L., Tang, M. B. Y., et al. (2011). Angiopoietin-like 4 regulates epidermal differentiation. PLoS ONE 6(9): e25377.
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10220/7135
dc.description.abstract 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.
dc.format.extent 51 p.
dc.language.iso en
dc.relation.ispartofseries PLoS ONE
dc.rights © 2011 The Author(s).
dc.subject DRNTU::Science::Biological sciences::Human anatomy and physiology.
dc.title Angiopoietin-like 4 regulates epidermal differentiation
dc.type Journal Article
dc.contributor.school School of Biological Sciences
dc.description.version Published version
dc.identifier.rims 161770

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