Expressional changes in the intracellular melanogenesis pathways and their possible role the pathogenesis of vitiligo

Kingo, Külli; Aunin, Eerik; Karelson, Maire; Rätsep, Ranno; Silm, Helgi; Vasar, Eero; Kõks, Sulev

doi:10.1016/j.jdermsci.2008.03.013

Cited by 36 publications

(45 citation statements)

References 37 publications

(45 reference statements)

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“…(20,30). In the present study we found statistically significant expressional downregulation of TYR and T(Y)RP1 mRNA, genes involved in melanin synthesis, in lesional and non-lesional skin of psoriasis patients compared with healthy controls.…”

Section: Resultssupporting

confidence: 62%

“…Tyrosinaserelated protein 1 (TYRPl)anddopachrometautomerase (DCT) are additional melanogenesis enzymes. The signal from the CRH-POMC system in human melanocytes reaches the melanogenesis enzymes TYR, TYRPl and DCT over MCIR through cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway and it is modulated by Wnt and MAPK (mitogen-activated protein kinase) pathways (17,20). ASIP is an antagonist of human MCIR.…”

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confidence: 99%

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Gene Expression Analysis of the Corticotrophin-releasing Hormone-proopiomelanocortin System in Psoriasis Skin Biopsies

Loite¹,

Kingo²,

Reimann³

et al. 2013

Acta Derm Venerol

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The corticotrophin-releasing hormone-proopiomelanocortin (CRH-POMC) system in the skin coordinates pigmentation and the immune response. The aim of this study was to evaluate the regulatory role of the neuroendocrine system in the pathogenesis of psoriasis. Using quantitative real-time-PCR, mRNA expression levels of 15 genes related to the CRH-POMC system were measured in punch biopsies from lesional and non-lesional skin of patients with psoriasis and from skin of healthy control subjects. Statistically significant up-regulation of POMC, CRH receptor type 1, melanin-concentrating hormone receptor (MCHR1) and melanocortin receptors 2, 3 and 4 mRNA expression in lesional and in non-lesional skin compared with healthy control samples were established. Tyrosinase (TYR), T(Y)RP-1 and ASIP genes were statistically significantly down-regulated in lesional and non-lesional skin of psoriasis samples compared with healthy subjects. The up-regulation of POMC, melanocortin receptors, CRH receptor type 1 and MCHR1 in the lesional and non-lesional skin of psoriasis patients supports the importance of the local CRH-POMC system in the pathogenesis of psoriasis.

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Section: Resultssupporting

confidence: 62%

mentioning

confidence: 99%

Gene Expression Analysis of the Corticotrophin-releasing Hormone-proopiomelanocortin System in Psoriasis Skin Biopsies

Loite¹,

Kingo²,

Reimann³

et al. 2013

Acta Derm Venerol

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“…These findings are consistent with elevated levels of apoptotic (TUNEL+) cells in the melanocyte region of growing feathers from vitiliginous SL chickens (particularly during active depigmentation) compared to non-vitiliginous SL, BL and LBL controls [17]. The mechanism of apoptosis was also indicated by decreased levels of anti-apoptotic protein Bcl2 in lesional skin compared to nonlesional skin of vitiligo patients [51,52]. …”

Section: Discussionsupporting

confidence: 66%

Understanding mechanisms of vitiligo development in Smyth line of chickens by transcriptomic microarray analysis of evolving autoimmune lesions

et al. 2012

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BackgroundThe Smyth line (SL) of chicken is an excellent avian model for human autoimmune vitiligo. The etiology of vitiligo is complicated and far from clear. In order to better understand critical components leading to vitiligo development, cDNA microarray technology was used to compare gene expression profiles in the target tissue (the growing feather) of SL chickens at different vitiligo (SLV) states.ResultsCompared to the reference sample, which was from Brown line chickens (the parental control), 395, 522, 524 and 526 out of the 44 k genes were differentially expressed (DE) (P ≤ 0.05) in feather samples collected from SL chickens that never developed SLV (NV), from SLV chickens prior to SLV onset (EV), during active loss of pigmentation (AV), and after complete loss of melanocytes (CV). Comparisons of gene expression levels within SL samples (NV, EV, AV and CV) revealed 206 DE genes, which could be categorized into immune system-, melanocyte-, stress-, and apoptosis-related genes based on the biological functions of their corresponding proteins. The autoimmune nature of SLV was supported by predominant presence of immune system related DE genes and their remarkably elevated expression in AV samples compared to NV, EV and/or CV samples. Melanocyte loss was confirmed by decreased expression of genes for melanocyte related proteins in AV and CV samples compared to NV and EV samples. In addition, SLV development was also accompanied by altered expression of genes associated with disturbed redox status and apoptosis. Ingenuity Pathway Analysis of DE genes provided functional interpretations involving but not limited to innate and adaptive immune response, oxidative stress and cell death.ConclusionsThe microarray results provided comprehensive information at the transcriptome level supporting the multifactorial etiology of vitiligo, where together with apparent inflammatory/innate immune activity and oxidative stress, the adaptive immune response plays a predominant role in melanocyte loss.

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“…Reactions were carried out in 10 μl reaction volumes in four replicates. Data is presented as 2 -ΔCT calculated in relation to the HPRT-1 [15] and statistical analysis was performed by using t-test. For analysis of functional significance of promoter genotype in the regulation of gene expression, we used subjects (n = 52) from whom both genomic DNA and skin biopsy was available.…”

Section: Methodsmentioning

confidence: 99%

Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

et al. 2010

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BackgroundMYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim was to examine nine known polymorphisms in the MYG1 gene, to investigate their functionality, and to study their association with vitiligo susceptibility.MethodsNine single nucleotide polymorphisms (SNPs) in the MYG1 locus were investigated by SNPlex assay and/or sequencing in vitiligo patients (n = 124) and controls (n = 325). MYG1 expression in skin biopsies was detected by quantitative-real time PCR (Q-RT-PCR) and polymorphisms were further analysed using luciferase and YFP reporters in the cell culture.ResultsControl subjects with -119G promoter allele (rs1465073) exhibited significantly higher MYG1 mRNA levels than controls with -119C allele (P = 0.01). Higher activity of -119G promoter was confirmed by luciferase assay. Single marker association analysis showed that the -119G allele was more frequent in vitiligo patients (47.1%) compared to controls (39.3%, P < 0.05, OR 1.37, 95%CI 1.02-1.85). Analysis based on the stage of progression of the vitiligo revealed that the increased frequency of -119G allele occurred prevalently in the group of patients with active vitiligo (n = 86) compared to the control group (48.2% versus 39.3%, P < 0.05; OR 1.44, 95%CI 1.02-2.03). Additionally, we showed that glutamine in the fourth position (in Arg4Gln polymorphism) completely eliminated mitochondrial entrance of YFP-tagged Myg1 protein in cell culture. The analysis of available EST, cDNA and genomic DNA sequences revealed that Myg1 4Gln allele is remarkably present in human populations but is never detected in homozygous state according to the HapMap database.ConclusionsOur study demonstrated that both MYG1 promoter polymorphism -119C/G and Arg4Gln polymorphism in the mitochondrial signal of Myg1 have a functional impact on the regulation of the MYG1 gene and promoter polymorphism (-119C/G) is related with suspectibility for actively progressing vitiligo.

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Expressional changes in the intracellular melanogenesis pathways and their possible role the pathogenesis of vitiligo

Cited by 36 publications

References 37 publications

Gene Expression Analysis of the Corticotrophin-releasing Hormone-proopiomelanocortin System in Psoriasis Skin Biopsies

Gene Expression Analysis of the Corticotrophin-releasing Hormone-proopiomelanocortin System in Psoriasis Skin Biopsies

Understanding mechanisms of vitiligo development in Smyth line of chickens by transcriptomic microarray analysis of evolving autoimmune lesions

Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

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