Disease relevance of Ivl

• In addition to the expression of suprabasal markers such as cytokeratin 10 and involucrin, carcinomas also express cytokeratin 8 and 18 [1].
• To study the role of IFN-gamma in the pathogenesis of inflammatory skin diseases, we used the involucrin promoter to overexpress IFN-gamma in the suprabasal layers of transgenic mouse epidermis [2].
• In addition, we evaluated pivotal keratinocyte functions necessary for the reparative hyperplasia, including proliferation by 5-bromo-2'deoxy-uridine labeling and differentiation by the expression of involucrin, keratin 1, and keratin 6 [3].

High impact information on Ivl

• We have used the involucrin promoter to overexpress IFN-gamma in the suprabasal layers of transgenic mouse epidermis [4].
• To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter [5].
• Involucrin is synthesized in abundance during terminal differentiation of keratinocytes [6].
• Involucrin is a substrate for transglutaminase and one of the precursors of the cross-linked envelopes present in the corneocytes of the epidermis and other stratified squamous epithelia [6].
• We have generated mice lacking involucrin from embryonic stem cells whose involucrin gene had been ablated by homologous recombination [6].

Biological context of Ivl

• RESULTS: The K14 and INV promoter constructs showed beta-galactosidase gene expression only in the epidermis, while the CMV promoter showed gene expression in both the dermis and epidermis [7].
• Lines from group I (CK2, 3, 5 and their ras-transfected homologous lines) shared a typical epithelial phenotype in monolayer and the ability (a) to form an epithelium similar to a CIN-III lesion and (b) to strongly express keratins K1-K10 and involucrin in organotypic cultures [8].
• Systematic repeat addition at a precise location in the coding region of the involucrin gene of wild mice reveals their phylogeny [9].
• Using beta-galactosidase as a reporter gene in transgenic mice, we observed specific activity of the involucrin promoter in the eyelid tip cells [10].
• PKC eta-induced differentiation is accompanied by the transcriptional activation of transglutaminase I, a key enzyme in squamous differentiation, and involucrin, a precursor of cornified envelopes [11].

Anatomical context of Ivl

• The transgenic animals express whn from the involucrin promoter, which is active in keratinocytes undergoing terminal differentiation [12].
• Finally, consistent with results of earlier studies, keratins 1, 10, 13, and 15, and filaggrin, involucrin, and loricrin were not detected at any stage of mammary gland development [13].
• In cell culture, the INV and K14 promoter constructs demonstrated significant beta-galactosidase expression in human keratinocytes, but minimal expression in 293 and NIH 3T3 cell types [7].
• The immunohistochemical profile of this rare type of tumour of the skin of mice, which includes a first-time description of involucrin expression, confirms the histological evidence of differentiation towards more than one segment of follicular epithelium [14].
• Western blot hybridization was performed to confirm the presence of involucrin in corneas [15].

Associations of Ivl with chemical compounds

• Involucrin, loricrin and the small proline-rich proteins (SPRRs) are precursors of the cornified envelope of terminally differentiated keratinocytes [16].
• The keratin 14 promoter targeted the receptor primarily to basal, proliferating keratinocytes; the involucrin (Inv) promoter targeted the receptor to suprabasal, differentiating keratinocytes [17].
• To examine this issue, transgenic mice in which the alpha2beta1 or alpha3beta1 integrin was expressed in the suprabasal epidermal layers via the involucrin promoter were subjected to skin carcinogenesis [18].
• Treatment of EDE with methylprednisolone or doxycycline reduced corneal permeability to OGD, improved corneal smoothness, and decreased involucrin and SPRR-2 immunoreactivity compared with EDE+PSS [19].

Co-localisations of Ivl

• The TGase 1 enzyme co-localized on the plasma membrane of migrating keratinocytes with involucrin, but not with loricrin, which suggests the premature assembly of the cornified envelope [20].

Regulatory relationships of Ivl

• Furthermore, in cultured human keratinocytes we have demonstrated that PPARalpha activators induce an increase in involucrin mRNA levels [21].
• We were therefore interested that a failure of eyelid fusion has been reported in mice that are homozygous null for the transforming growth factor alpha (TGF-alpha) gene and in mice (invalpha5beta1) in which a transgenic alpha5beta1 integrin under the control of the involucrin promoter is misexpressed in differentiating keratinocytes [10].
• Our results indicate that during differentiation of epidermal keratinocyte, PAI-2 expresses mainly in the more differentiated keratinocytes and may protect the terminal differentiated keratinocytes from prematuration through inhibiting involucrin expression in cornified envelope [22].
• To study the role of Notch1 in epidermal differentiation and the development of the various cell types within the mouse hair follicle, we generated transgenic mice that express a constitutive activated form of Notch1 under the control of the involucrin promoter [23].

Other interactions of Ivl

• Concurrently, there was diminished beta-glucocerebrosidase activity at the stratum granulosum-stratum corneum junction and a modest decrease in both involucrin and loricrin protein expression, markers of keratinocyte differentiation [24].
• Conversely, TAp63 transcribed the upper layer's genes (Ets-1, K1, transglutaminases, involucrin) [25].
• Analysis of the mice showed that no phenotypic effect was observed in mice expressing PAH and GTP-CH from the INV promoter [26].
• We have previously described a transgenic mouse model of epidermal neoplasia wherein expression of a switchable form of c-Myc, MycER(TAM), is targeted to the postmitotic suprabasal keratinocytes of murine epidermis via the involucrin promoter [27].
• The phenotypes examined include ODC enzymatic activity, doubling time, morphological change, anchorage dependent growth, tumorigenicity in nude mice, induction of epithelial differentiation marker protein (involucrin), and change of cell cycle position [28].

Analytical, diagnostic and therapeutic context of Ivl

• In addition, immunohistochemistry demonstrated that expression of the differentiation markers K1, K6, and involucrin were abnormal [29].
• Epidermal differentiation marker proteins such as involucrin, loricrin, and keratin1 were also increased in PS-treated NHEKs, by ELISA or Western blotting analysis [30].
• In nude mouse xenografts, keratinocyte transglutaminase, localized immunohistochemically with a biotinylated mouse monoclonal antibody, was again present only in a minority of the squamous lines whereas involucrin was expressed in all [31].
• To complement the immunoblot analysis, we also examined the distribution of each protein in basal (involucrin-negative) and suprabasal (involucrin-positive) cells in stratified colonies, using confocal microscopy [32].

References