Regulation of late cornified envelope genes relevant to psoriasis risk by plant-derived cyanidin

Austin, Heather R.; Hoss, Elika; Batie, Shane F.; Moffet, Eric W.; Jurutka, Peter W.; Haussler, Mark R.; Whitfield, G. Kerr

doi:10.1016/j.bbrc.2013.12.128

Cited by 17 publications

(19 citation statements)

References 29 publications

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“…In primary human keratinocyte culture, cyanidin (Cya) upregulated the expressions of LCE3A, LCE3B and LCE3E under conditions both at 60 mmol/L calcium (low calcium) and 1.2 mmol/L calcium (high calcium) (Austin et al, 2014). Tape stripping to induce superficial skin injury also upregulated LCE3A/3C/3D/3E expressions, and however, other LCE genes were expressed at moderate levels in normal skin, but were downregulated in psoriatic skin or superficial injury after tape stripping (Bergboer et al, 2011).…”

Section: Lce3bmentioning

confidence: 99%

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis: A Systematic Review

Shen

Gao

Yin

et al. 2015

Journal of Genetics and Genomics

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Section: Lce3bmentioning

confidence: 99%

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis: A Systematic Review

Shen

Gao

Yin

et al. 2015

Journal of Genetics and Genomics

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“…We have shown here that the presence of risk alleles caused overexpression of specific LCE3 genes. However, this is in sharp contrast to the fact that analogs of Vitamin D3 used to treat psoriasis (1,25-dihydroxyvitamin D3) functions by increasing LCE3 expression, which subsequently heals the disease 35 . Higher LCE3 expression thus appears as protective.…”

Section: Discussionmentioning

confidence: 89%

“…LCE3 gene cluster spans ~60 kb and comprises five genes (LCE3A, 3B, 3C, 3D and 3E) within the EDC (PSORS4) at chromosome 1q21. Because of the strategic role of these genes in epidermal barrier repair and their reported upregulation in psoriatic skin 34 , many later studies focused on the LCE3 genes 35 36 37 38 39 . It has previously been demonstrated that the expression of LCE3 genes were markedly induced after superficial injury of the normal skin 34 40 .…”

mentioning

confidence: 99%

Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk alleles in Indian population

Chandra

Lahiri

Senapati³

et al. 2016

Sci Rep

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HLA-Cw6 is one of the most associated alleles in psoriasis. Recently, Late Cornified Envelop 3 (LCE3) genes were identified as a susceptibility factor for psoriasis. Some population showed epistatic interaction of LCE3 risk variants with HLA-Cw6, while some population failed to show any association. We determined the associations of a 32.2 kb deletion comprising LCE3C-3B genes and three SNPs (rs1886734, rs4112788; rs7516108) at the LCE3 gene cluster among the psoriasis patients in India. All three SNPs at the LCE3 gene cluster failed to show any association. In contrary, for patients with HLA-Cw6 allele, all three SNPs and the LCE3C-3B deletion showed significant associations. While, all five LCE3 genes were upregulated in psoriatic skin, only LCE3A showed significant overexpression with homozygous risk genotype compared to the non-risk genotype. LCE3B also showed significant overexpression in patients with HLA-Cw6 allele. Moreover, LCE3A showed significantly higher expression in patients bearing homozygous risk genotype in presence of HLA-Cw6 allele but not in those having non-risk genotype, demonstrating the combined effect of HLA-Cw6 allele and risk associated genotype near LCE3A gene. Integration of genetic and gene expression data thus allowed us to identify the actual disease variants at the LCE3 cluster among the psoriasis patients in India.

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“…The endocrine VDR ligand (1,25D), as well as novel VDR ligands delphinidin and cyanidin, have previously been shown to upregulate LCE3 gene expression to some extent [ 11 , 12 ]. Further, a VDRE has been identified adjacent to the LCE3A gene [ 11 ] and is not affected by the LCE3C_LCE3B deletion ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Bioactive Dietary VDR Ligands Regulate Genes Encoding Biomarkers of Skin Repair That Are Associated with Risk for Psoriasis

et al. 2018

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Treatment with 1,25-dihydroxyvitamin D3 (1,25D) improves psoriasis symptoms, possibly by inducing the expression of late cornified envelope (LCE)3 genes involved in skin repair. In psoriasis patients, the majority of whom harbor genomic deletion of LCE3B and LCE3C (LCE3C_LCE3B-del), we propose that certain dietary analogues of 1,25D activate the expression of residual LCE3A/LCE3D/LCE3E genes to compensate for the loss of LCE3B/LCE3C in the deletant genotype. Herein, human keratinocytes (HEKn) homozygous for LCE3C_LCE3B-del were treated with docosahexaenoic acid (DHA) and curcumin, two low-affinity, nutrient ligands for the vitamin D receptor (VDR). DHA and curcumin induce the expression of LCE3A/LCE3D/LCE3E mRNAs at concentrations corresponding to their affinity for VDR. Moreover, immunohistochemical quantitation revealed that the treatment of keratinocytes with DHA or curcumin stimulates LCE3 protein expression, while simultaneously opposing the tumor necrosis factor-alpha (TNFα)-signaled phosphorylation of mitogen activated protein (MAP) kinases, p38 and Jun amino-terminal kinase (JNK), thereby overcoming inflammation biomarkers elicited by TNFα challenge. Finally, DHA and curcumin modulate two transcription factors relevant to psoriatic inflammation, the activator protein-1 factor Jun B and the nuclear receptor NR4A2/NURR1, that is implicated as a mediator of VDR ligand-triggered gene control. These findings provide insights into the mechanism(s) whereby dietary VDR ligands alter inflammatory and barrier functions relevant to skin repair, and may provide a molecular basis for improved treatments for mild/moderate psoriasis.

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Regulation of late cornified envelope genes relevant to psoriasis risk by plant-derived cyanidin

Cited by 17 publications

References 29 publications

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis: A Systematic Review

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis: A Systematic Review

Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk alleles in Indian population

Bioactive Dietary VDR Ligands Regulate Genes Encoding Biomarkers of Skin Repair That Are Associated with Risk for Psoriasis

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