Inhibition of Epidermal Terminal Differentiation and Tumour Promotion by Retinoids

Lichti, Ulrike; Yuspa, Stuart H.

doi:10.1002/9780470720943.ch6

Cited by 7 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To know the molecular mechanism of the transdifferentiation induced by RA, we established a culture system where RA induced epidermal transdifferentiation accompanying the expression of markers of esophagus epithelium using rat embryonic skin, as it is easier than chick embryonic skin in immunohistochemical analysis. Then, we studied about cooperative interplay of Gbx1, TG2/Gh and TGF-b2 as they are reported to be induced individually by RA in cultures of chick embryonic skin (Obinata et al, 2001), mouse epidermal cells (Lichti and Yuspa 1985a) and human hair follicles (Foitzik et al, 2005) respectively. Studies of Gbx1 have concentrated on the brain or neurons (Rhinn et al, 2004;Asbreuk et al, 2002) and are poor in other tissues.…”

Section: Introductionmentioning

confidence: 99%

Tgm2/Gh, Gbx1 and TGF-beta are involved in retinoic acid-induced transdifferentiation from epidermis to mucosal epithelium

Obinata¹,

Osakabe²,

Yamaguchi³

et al. 2011

Int. J. Dev. Biol.

View full text Add to dashboard Cite

�e previousl� demonstrated that retinoic acid �RA� induces epidermis to transdifferen�e previousl� demonstrated that retinoic acid �RA� induces epidermis to transdifferentiate to mucosal epithelium with goblet cells in chick embr�onic cultured skin. To characterize the molecular mechanism of this transdifferentiation process, we used rat embr�onic cultured skin and immunohistochemistr� to confirm that RA-induced epidermal transdifferentiation accompanies the expression of markers of esophagus epithelium. Because Gbx1, TG2/Gh �transglutaminase2� and TGF-b2 are reported individuall� to be induced b� RA in cultures of chick embr�onic skin, mouse epidermal cells and human hair follicles respectivel�, here, we investigated whether cooperative interpla� of Gbx1, TG2/Gh and TGF-b2 is required for the transdifferentiation of epidermal cells to mucosal cells. �e have shown that expression of Gbx1, TG2/Gh and TGF-b proteins were all upregulated in RA-induced transdifferentiated skin and that the former two were expressed in the epidermis, while TGF-b was expressed in the dermis. Inhibitors of the TGF-b signal pathwa� partiall� inhibited transdifferentiation. Overexpression of both hTG2/Gh and mGbx1 together in the epidermis b� electroporation resulted in cuboidal cells in the upper cell la�ers of the epidermis without keratinized la�ers, although epidermal keratinization was observed in skin b� overexpression of either of them. Labeling DNA with BrdU indicated that RA directl� transdifferentiated transient amplif�ing epidermal cells, not stem cells, to mucosal cells. This stud� showed that coexpression of TG/2 and Gbx1 in the epidermis was required for esophagus-like mucosal transdifferentiation, and that increase in TGF-b2 expression b� RA in the dermis was essential to induce transdifferentiation through epithelial-mesench�mal interaction.

show abstract

Section: Introductionmentioning

confidence: 99%

Tgm2/Gh, Gbx1 and TGF-beta are involved in retinoic acid-induced transdifferentiation from epidermis to mucosal epithelium

Obinata¹,

Osakabe²,

Yamaguchi³

et al. 2011

Int. J. Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…We focused on three genes, i.e., Tgm2, Gbx1, and TGF-β, because we [21] and others [61,62] showed these genes are induced by RA. At first we examined the expression of two of them, Tgm2 and Gbx1, in rat embryonic skin.…”

Section: Atra Increases Expression Of Tgm2 and Gbx1 Mrna And Protein mentioning

confidence: 99%

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

Akimoto

Miyaji

Morimoto-Kamata

et al. 2014

JDB

View full text Add to dashboard Cite

Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470-488). However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA) for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal OPEN ACCESS J. Dev. Biol. 2014, 2 159 epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA) play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

show abstract

“…5) The most characteristic enzyme function of the class of enzymes known as TG is the formation of covalent bonds between epsilon amino groups of primary amines (lysine or others) and the gamma-carboxyamine group of glutamine residues of proteins, resulting polymerization. 6) Transglutaminase 1, 3 and 5 found in the keratinocyte 6) are members of transglutaminase family and play an important role in the formation of the stratum corneum in the epidermis of skin by the introduction of g-glutamyl-elysyl isopeptide bond cross-links into proteins.…”

mentioning

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

View full text Add to dashboard Cite

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.

show abstract

Inhibition of Epidermal Terminal Differentiation and Tumour Promotion by Retinoids

Cited by 7 publications

References 36 publications

Tgm2/Gh, Gbx1 and TGF-beta are involved in retinoic acid-induced transdifferentiation from epidermis to mucosal epithelium

Tgm2/Gh, Gbx1 and TGF-beta are involved in retinoic acid-induced transdifferentiation from epidermis to mucosal epithelium

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

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

Contact Info

Product

Resources

About