Type I Keratinocyte Transglutaminase: Expression in Human Skin and Psoriasis

Schroeder, W. T.; Thacher, Scott M.; Stewart-Galetka, Shelley; Annarella, Mary; Chema, Deidra; Siciliano, Michael J.; Davies, Peter J.; Tang, Hsiao Yuan; Sowa, Blair A.; Duvic, Madeleine

doi:10.1111/1523-1747.ep12611394

Cited by 92 publications

(51 citation statements)

References 42 publications

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“…We show that this region directs expression of the transgene to the suprabasal layers, comprising the late spinous and granular layers, of several squamous tissues. This pattern of expression correlates well with that reported for TGase I (47,48). Deletion analysis identified two DNA elements in the 2.9-kb regulatory region containing an Sp1-and a CREB/AP-1-like site that are involved in the transcriptional regulation of TGase I.…”

supporting

confidence: 86%

Regulation of the Transglutaminase I Gene

Medvedev

Saunders²,

Matsuura

et al. 1999

Journal of Biological Chemistry

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The transglutaminase I (TGase I) gene encodes an enzyme that catalyzes the cross-linking of structural proteins involved in the formation of the cornified envelope during squamous cell differentiation. To identify DNA elements important for the transcriptional control of the TGase I gene, we analyzed the ability of a 2.9-kilobase pair (kb) upstream regulatory region to control the expression of a reporter gene in vivo and in vitro. Transgenic mice bearing the pTG(؊2.9kb)CAT construct exhibited the same pattern of tissue-specific expression of CAT as reported for TGase I. Deletion analysis in transiently transfected rabbit tracheal epithelial cells indicated that two sequences from bp ؊490 to ؊470 and from ؊54 to ؊37 are involved in the activation of TGase I transcription. Point mutation analysis and mobility shift assays showed that the sequence located between ؊54 and ؊37 is a functional Sp1-like transcription element. Sp1 and Sp3, but not Sp2, are part of nuclear protein complexes from differentiated RbTE cells binding to this site. The element TGATGTCA between bp ؊490 and ؊470 is contained in a larger 22-bp palindrome and resembles the consensus cAMP response elementbinding protein (CREB)/AP-1 element recognized by dimeric complexes of members of the CREB, ATF, Fos, and Jun families. Mutations in this sequence greatly reduced promoter activity. Supershift analysis identified CREB1, JunB, c-Fos, Fra-1, and c-Jun in protein complexes isolated from differentiated rabbit tracheal epithelial cells binding to this site. Our study shows that the Sp1-and CREB/AP-1-like sites act in concert to stimulate transcription of the TGase I gene. The 2.9-kb promoter region could guide expression of specific genes in the granular layer of the epidermis and could be useful in gene therapy.

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supporting

confidence: 86%

Regulation of the Transglutaminase I Gene

Medvedev

Saunders²,

Matsuura

et al. 1999

Journal of Biological Chemistry

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“…Thus, only some differentiation proteins (i.e., K10, loricrin, filaggrin) were found to be altered in in vitro reconstructed XP epidermis. Although there are major clinical and histogical differences between XP and the human hyperproliferative syndrome psoriasis, the delayed and reduced expression of K10 (25), loricrin (26), and filaggrin and slightly affected transglutaminase (27,28) have also been found in skin biopsies taken from patients with psoriasis.…”

Section: Resultsmentioning

confidence: 99%

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skininvitro

Bernerd

Asselineau

Vioux

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Sun exposure has been clearly implicated in premature skin aging and neoplastic development. These features are exacerbated in patients with xeroderma pigmentosum (XP), a hereditary disease, the biochemical hallmark of which is a severe deficiency in the nucleotide excision repair of UV-induced DNA lesions. To develop an organotypic model of DNA repair deficiency, we have cultured several strains of primary XP keratinocytes and XP fibroblasts from skin biopsies of XP patients. XP skin comprising both a fullthickness epidermis and a dermal equivalent was succesfully reconstructed in vitro. Satisfactory features of stratification were obtained, but the expression of epidermal differentiation products, such as keratin K10 and loricrin, was delayed and reduced. In addition, the proliferation of XP keratinocytes was more rapid than that of normal keratinocytes. Moreover, increased deposition of cell attachment proteins, ␣-6 and ␤-1 integrins, was observed in the basement membrane zone, and ␤-1 integrin subunit, the expression of which is normally confined to basal keratinocytes, extended into several suprabasal cell layers. Most strikingly, the in vitro reconstructed XP skin displayed numerous proliferative epidermal invasions within dermal equivalents. Epidermal invasion and higher proliferation rate are reminiscent of early steps of neoplasia. Compared with normal skin, the DNA repair deficiency of in vitro reconstructed XP skin was documented by long-lasting persistence of UVB-induced DNA damage in all epidermal layers, including the basal layer from which carcinoma develops. The availability of in vitro reconstructed XP skin provides opportunities for research in the fields of photoaging, photocarcinogenesis, and tissue therapy.three-dimensional skin model ͉ xeroderma pigmentosum ͉ UVB radiation ͉ DNA damage ͉ keratinocyte differentiation

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“…The synthesis of TGase 1 is regulated in cultured keratinocytes by various stimuli, including phorbol esters, retinoids and corticosteroids (Floyd and Jetten, 1989;Liew and Yamanishi, 1992;Yamada et al, 1994) and by intercellular Ca 2 + c o n c e n t r a t i o n s , presumably by AP-1 mediated gene regulatory signals (Dlugosz and Yuspa, 1994;Mariniello et al, 1995). In epithelia such as the epidermis, TGase 1 expression is induced shortly after commitment to terminal d i fferentiation (Michel et al, 1992), although a minor degree of TGase 1 expression is detectable in u n d i fferentiated basal keratinocytes (Schroeder et al , 1992;Kim et al, 1995a). The bulk of the TGase 1 enzyme is bound to the plasma membranes by its constitutively N-and S-fatty acylated 10 kDa amino terminal part (Rice et al, 1990;Phillips et al, 1993;Steinert et al, 1996a).…”

Section: The Tgasesmentioning

confidence: 99%