Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair

Koning, Heleen D. de; Bogaard, E.H.J. van den; Bergboer, Judith G.M.; Kamsteeg, Marijke; Vlijmen-Willems, Ivonne M.J.J. van; Hitomi, Kiyotaka; Henry, Julie; Simon, Michel; Takashita, N.; Ishida‐Yamamoto, Akemi; Schalkwijk, Joost; Zeeuwen, Patrick L.J.M.

doi:10.1111/j.1365-2133.2012.10885.x

Cited by 74 publications

(73 citation statements)

References 52 publications

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“…Thus, they are considered a marker of the aberrant differentiation and proliferation of keratinocytes. It has been reported that SPRR protein was up-regulated following skin barrier disruption in the lesions of atopic dermatitis and psoriatic skin [40,41,42]. KLK6 is involved in the proteolysis of corneodesmosome, which cleaves desmoglein 1 [43].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in Melasma in Korean Women

Chung¹,

Noh²,

Yang³

et al. 2014

Dermatology

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Background: There has been a paucity of data about the difference in gene expression between melasma lesional skin and normal adjacent one. Objective: Our aim was to identify novel genes involved in the pathogenesis of melasma. Methods: We performed a microarray analysis and confirmed the results on quantitative real-time polymerase chain reaction (qRT-PCR) in Korean women with melasma. Results: There were 334 genes whose degree of expression showed a significant difference between melasma lesional skin and normal adjacent one. Of these, five were confirmed on qRT-PCR. In melasma lesional skin, there were down-regulation of genes involved in the PPAR signaling pathway and up-regulation of genes involved in neuronal component and the functions of stratum corneum barrier. Conclusion: This result suggests that the pathogenesis of melasma might be associated with novel genes involved in the above signaling pathway in Korean women.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in Melasma in Korean Women

Chung¹,

Noh²,

Yang³

et al. 2014

Dermatology

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“…All of these biological functions are important for tissue growth, maintaining epithelial barrier integrity, and downregulating the inflammatory response. For example, cornifin B, cornulin, desmoglein 3,and cystatins are components of the epithelium that are important for generating and maintaining a cohesive keratinocyte barrier that is both flexible and yet impermeable (33)(34)(35)(36). Although serine protease inhibitors (serpins) aid in wound healing, epithelial damage repair, and the inhibition of inflammatory proteases, all of these functions contribute to a healthy, adherent, defensive barrier (37)(38)(39).…”

Section: Participant Characteristicsmentioning

confidence: 99%

Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility

Birse

Arnold

Novak

et al. 2015

J Virol

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The variable infectivity and transmissibility of HIV/SHIV has been recently associated with the menstrual cycle, with particular susceptibility observed during the luteal phase in nonhuman primate models and ex vivo human explant cultures, but the mechanism is poorly understood. Here, we performed an unbiased, mass spectrometry-based proteomic analysis to better understand the mucosal immunological processes underpinning this observed susceptibility to HIV infection. Cervicovaginal lavage samples (n ‫؍‬ 19) were collected, characterized as follicular or luteal phase using days since last menstrual period, and analyzed by tandem mass spectrometry. Biological insights from these data were gained using a spectrum of computational methods, including hierarchical clustering, pathway analysis, gene set enrichment analysis, and partial least-squares discriminant analysis with LASSO feature selection. Of the 384 proteins identified, 43 were differentially abundant between phases (P < 0.05, >2-fold change). Cell-cell adhesion proteins and antiproteases were reduced, and leukocyte recruitment (interleukin-8 pathway, P ‫؍‬ 1.41E-5) and extravasation proteins (P ‫؍‬ 5.62E-4) were elevated during the luteal phase. LASSO/PLSDA identified a minimal profile of 18 proteins that best distinguished the luteal phase. This profile included cytoskeletal elements and proteases known to be involved in cellular movement. Gene set enrichment analysis associated CD4؉ T cell and neutrophil gene set signatures with the luteal phase (P < 0.05). Taken together, our findings indicate a strong association between proteins involved in tissue remodeling and leukocyte infiltration with the luteal phase, which may represent potential hormone-associated mechanisms of increased susceptibility to HIV. IMPORTANCERecent studies have discovered an enhanced susceptibility to HIV infection during the progesterone-dominant luteal phase of the menstrual cycle. However, the mechanism responsible for this enhanced susceptibility has not yet been determined. Understanding the source of this vulnerability will be important for designing efficacious HIV prevention technologies for women. Furthermore, these findings may also be extrapolated to better understand the impact of exogenous hormone application, such as the use of hormonal contraceptives, on HIV acquisition risk. Hormonal contraceptives are the most widely used contraceptive method in sub-Saharan Africa, the most HIV-burdened area of the world. For this reason, research conducted to better understand how hormones impact host immunity and susceptibility factors important for HIV infection is a global health priority. The global HIV incidence rates for women remain high, so much so that every minute a young woman becomes infected with HIV (1). With infection rates twice as high for women aged 15 to 24 compared to their age-matched male counterparts, it is clear that young women are more susceptible to HIV infection (1, 2). Understanding biological contributors to HIV risk in women is therefore impo...

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“…However, impaired skin barrier function has also been shown in AD patients without FLG mutations [18] . Recently, the altered expression of genes encoding small proline-rich proteins and the LCE-like proline-rich 1 protein (LELP1) in the skin of AD patients has been documented [19,20] .…”

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confidence: 99%

Altered Expression of Genes Encoding Cornulin and Repetin in Atopic Dermatitis

Trzeciak¹,

Sakowicz-Burkiewicz

Wesserling

et al. 2017

Int Arch Allergy Immunol

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Background: It is assumed that beside alterations in the filaggrin gene (FLG), disturbances within genes encoding other cornified envelope proteins are also involved in atopic dermatitis (AD). To identify new potential markers of AD, we studied the polymorphisms of genes encoding repetin (RPTN), cornulin (CRNN), and their expression in the skin of AD patients. Methods: Polymorphisms in CRNN (rs941934), RPTN (rs284544, rs28441202, rs3001978, and rs12117644), and FLG mutations (R2447X, S3247X) were analyzed by TaqMan genotyping assay and by PCR-RFLP in the blood samples of 159 AD patients and 108 healthy subjects. The expression levels of CRNN and RPTN were determined by qRT-PCR in 34 AD skin samples (17 lesional and 17 nonlesional) and in 27 skin biopsies from healthy volunteers. The AD patients were recruited from the clinic of the university hospital between 2012 and 2014. Results:CRNN rs941934 (A allele) was associated with AD (OR 2.095, p = 0.008), a severe course of disease (p = 0.041), elevated IgE levels (p = 0.047), eosinophilia (p = 0.018), and concomitant asthma (p = 0.004). The mRNA level of CRNN was decreased in the AD skin (p = 0.041). In the AD patients without FLG mutations, the CC genotype of RPTN rs3001978 was associated with AD (OR 0.39, p = 0.037), early age at onset (p = 0.033), pruritus (p = 0.021), severity of AD (p = 0.045), and concomitant asthma (p = 0.041). The elevated mRNA levels of RPTN in lesional (p < 0.001) and nonlesional (p = 0.017) AD skin were observed. Conclusions: The single-nucleotide polymorphisms of CRNN (rs941934) and RPTN (rs3001978, rs28441202) may contribute to AD development, but further studies on a larger group of AD patients are needed to verify this assumption.

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Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair

Abstract: Skin barrier disruption induces a temporary barrier repair response composed of increased expression of several cornification-related proteins, and decreased expression of some structural and desquamation-related proteins.

Cited by 74 publications

References 52 publications

Gene Expression Profiling in Melasma in Korean Women

Gene Expression Profiling in Melasma in Korean Women

Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility

Altered Expression of Genes Encoding Cornulin and Repetin in Atopic Dermatitis

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