Expression and Regulation of Cornified Envelope Proteins in Human Corneal Epithelium

Tong, Louis; Corrales, Rosa M.; Chen, Zhuo; Villarreal, Arturo; Paiva, Cintia S. de; Beuerman, Roger W.; Li, Dequan; Pflugfelder, Stephen C.

doi:10.1167/iovs.05-1129

Cited by 73 publications

(74 citation statements)

References 47 publications

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“…Monodansylcadaverine (MDC) (Sigma) was used as a cell-permeable transglutaminase competitive inhibitor. 16) In some cases, 40 mM MDC was added throughout the culture.…”

Section: Methodsmentioning

confidence: 99%

Transdifferentiation of Epidermis to Mucous Epithelium by Retinol Accompanies Increase in Transglutaminase 2/Gh and Decrease in Transglutaminase 3

Obinata

Akimoto

2011

Biological & Pharmaceutical Bulletin

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We showed previously that transdifferentiation of skin epidermis to mucous epithelium can be induced by treatment with 20 m mM retinol for 1 d followed by culture for 4 d without retinol in chick embryonic tarsometatarsal skin. In mouse epidermal cells, 3 m mM retinoic acid (an active metabolite of retinol) inhibits epidermal keratinization in consistent with an increase in transglutaminase (TG)2/Gh, while its physiological role in the skin is still unresolved. TG1, TG3 and TG5 are also found in mammalian keratinocytes and play an important role in the formation of the stratum corneum in the skin by the introduction of cross-links into proteins. The most characteristic enzyme function of TG family is calcium-dependent transamidation activity (transamidase) that introduces inter or intramolecular e e-(g g-glutamyl)lysine cross-links into the protein. TG2/Gh is a multifunctional protein and ubiquitously expressed member of transglutaminase family that has been implicated in a variety of biological processes. By in situ hybridization analysis, we showed that TG2/Gh mRNA expression started to increase throughout the skin during the culture for 1 d with retinol, while it was weak in the control skin. On the other hand, an expression of TG3 mRNA was increased in the keratinized epidermis of control skin but was decreased by retinol. In situ transamidase activity of transglutaminase was weak in retinol-pretreated skin. Therefore, it was indicated that functions other than transamidase of TG2/Gh protein might be important in retinolinduced epidermal mucous transdifferentiation.

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“…Monodansylcadaverine (MDC) (Sigma) was used as a cell-permeable transglutaminase competitive inhibitor. 16) In some cases, 40 mM MDC was added throughout the culture.…”

Section: Methodsmentioning

confidence: 99%

Transdifferentiation of Epidermis to Mucous Epithelium by Retinol Accompanies Increase in Transglutaminase 2/Gh and Decrease in Transglutaminase 3

Obinata

Akimoto

2011

Biological & Pharmaceutical Bulletin

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“…11,34 To analyze the expression response of such biomarkers in our immortalized corneal epithelial keratinocytes exposed to different microenvironments, we employed RT 2 -PCR (qPCR) for the stem cell marker ABCG2, 35 for terminal differentiation markers filaggrin (FIL) and involucrin (INV), 34 CK19 and CK12, discriminating less from progressively differentiated cell stages, 36 as well as for the proliferation marker Ki-67 (MKI67). 37 In addition to the holistic and nonholistic natural cell microenvironments, we detected the status of mRNA transcription levels also in solitary grown corneal keratinocytes at the respective time points, to obtain information about auto-and paracrine-mediated keratinocyte self-regulation of biomarker gene expression, that is, the autonomous cornea epithelial cell base situation.…”

Section: Gene Expression Revealed Microenvironmental Regulation Of Tymentioning

confidence: 99%

Natural Corneal Cell-Based Microenvironment as Prerequisite for Balanced 3D Corneal Epithelial Morphogenesis: A Promising Animal Experiment-Abandoning Tool in Ophthalmology

Schulz

Beck

Laird

et al. 2014

Tissue Engineering Part C: Methods

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To achieve durable recognition as a promising animal experiment-abandoning tool in ophthalmology, in vitro engineered tissue equivalents of the human cornea should exhibit proper morphogenesis. Regarding this issue, we were seeking for the natural cell microenvironment fulfilling the minimum requirements to allow human corneal keratinocytes to develop a balanced epithelial morphology with regular spatial appearance of tissue homeostatic biomarkers. Hence, we established cocultures of 3D cell-based collagen scaffolds comprising immortalized corneal keratinocytes combined with a gradual cornea-derived in vivo-like cell microenvironment, together with immortalized stromal fibroblasts alone (nonholistic) or fibroblasts and immortalized endothelial cells (holistic). With matched non-holistic microenvironments revealing mostly flattened cells and putative apical cell ablation foci at day 6, and 9 in HE stains, holistic counterparts yielded proper epithelial stratification with cell flattening restricted to apical layers. Concordantly, RT 2 -PCR showed a tremendous increase in gene expression for progressive and terminal biomarkers of corneal keratinocyte differentiation, cytokeratin (CK) 12, and filaggrin (FIL), in response to nonholistic environments, while involucrin (INV) was moderately but significantly upregulated. Although visible, this increase was moderate in corneal keratinocytes with a holistic environment. On the protein level, indirect immunofluorescence revealed that only epithelia of holistic environments showed diminishment in CK19, counteracted by CK12 rising over time. This time-dependent progression in differentiation coincided with declined proliferation and tissue-regular focus of differentiation biomarkers inv and fil to suprabasal and apical cell layers. Our novel findings suggest the interplay of native tissue forming cell entities, important for balanced corneal epithelial morphogenesis. In addition, they provide evidence for a holistic cell microenvironment as a prerequisite for development of an in vitro engineered corneal epithelial tissue equivalent, exhibiting a regular appearance of tissue homeostatic biomarkers. Such equivalents will be promising tools in ophthalmology, for example, for mechanistic studies in basic research and/or testing of generics or preclinical validation of innovative cornea-tailored biomaterials, desired for regenerative strategies.

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“…The SPRR gene class consists of two SPRR1 and seven SPRR2 genes, along with a single SPRR3 gene (Kartasova & van de Putte 1988). In human cornea tissue, the expression of SPRR1, SPRR2 and filaggrin protein were detected in the central and peripheral corneal and limbal epithelium (Tong et al 2006). Cabral et al noticed that the structural organization and regulation of the SPRR gene family reflects the epithelial barrier's role i.e.…”

Section: Role Of the Skin Barriermentioning

confidence: 99%

Role of genetic aspect in pathogenesis of atopic dermatitis

Wesserling

2013

biologica

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The pathogenesis of atopic dermatitis (AD) is a very complicated process that involves an intricate array of molecules. Nowadays it is generally accepted that cytokines play an important role in the progression of the clinical presentation of atopic dermatitis. However, emerging data point to the possible involvement of cornified envelope proteins in the development of skin barrier dysfunction and illness. Unfortunately, our knowledge on relation of particular genotype to progression of AD is very limited. Therefore, intensive studies are needed to increase our understanding of genetic background of atopic dermatitis. Hopefully the future research will identify new factors that help us to determine the additional risk for certain patients with atopic dermatitis.

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Expression and Regulation of Cornified Envelope Proteins in Human Corneal Epithelium

Cited by 73 publications

References 47 publications

Transdifferentiation of Epidermis to Mucous Epithelium by Retinol Accompanies Increase in Transglutaminase 2/Gh and Decrease in Transglutaminase 3

Transdifferentiation of Epidermis to Mucous Epithelium by Retinol Accompanies Increase in Transglutaminase 2/Gh and Decrease in Transglutaminase 3

Natural Corneal Cell-Based Microenvironment as Prerequisite for Balanced 3D Corneal Epithelial Morphogenesis: A Promising Animal Experiment-Abandoning Tool in Ophthalmology

Role of genetic aspect in pathogenesis of atopic dermatitis

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