M.G. Mahoney

Novel member of the mouse desmoglein gene family: Dsg1-β

Abstract: Desmosomes are major intercellular adhesion junctions that provide stable cell–cell contacts and mechanical strength to epithelial tissues by anchoring cytokeratin intermediate filaments of adjacent cells. Desmogleins (Dsg) are transmembrane core components of the desmosomes, and belong to the cadherin supergene family of calcium‐dependent adhesion molecules. Currently, there are three known isoforms of Dsgs (Dsg1, Dsg2, and Dsg3), encoded by distinct genes that are differentially expressed to determine their tissue specificity and differentiation state of epithelial cells. In this study, we cloned a novel mouse desmoglein gene sharing high homology to both mouse and human Dsg1. We propose to designate the previously published mouse Dsg1 gene as Dsg1‐α and the new gene as Dsg1‐β. Analysis of intron/exon organization of the Dsg1‐α and Dsg1‐β genes revealed significant conservation. The full‐length mouse Dsg1‐β cDNA contains an open reading frame of 3180 bp encoding a precursor protein of 1060 amino acids. Dsg1‐β protein shares 94% and 76% identity with mouse Dsg1‐α and human DSG1, respectively. RT‐PCR using a multitissue cDNA panel demonstrated that while Dsg1‐α mRNA was expressed in 15‐ to 17‐day‐old embryos and adult spleen and testis, Dsg1‐β mRNA was detected in 17‐day‐old embryos only. To assess subcellular localization, a FLAG‐tagged expression construct of Dsg1‐β was transiently expressed in epithelial HaCaT cells. Dsg1‐β‐FLAG was found at the cell–cell border and was recognized by the anti‐Dsg1/Dsg2 antibody DG3.10. In summary, we have cloned and characterized a novel member of the mouse desmoglein gene family, Dsg1‐β.

Extracellular matrix in cutaneous ageing: the effects of 0.1% copper-zinc malonate-containing cream on elastin biosynthesis.

Abstract:  Cutaneous ageing, as visualized at the exposed areas of skin, reflects dramatic alterations in the structure and function of the extracellular matrix of connective tissues. Among them, the elastic fibre network, which is responsible for the physiological elasticity and resilience of normal skin, undergoes degradative changes leading to loss of functional elastic fibres. A potential strategy to counteract these degenerative changes entails topical application of a compound that may lead to regeneration of the elastic fibre network. In this study, we have evaluated the effects of a bi‐metal, 0.1% copper–zinc malonate‐containing cream that has been shown to efface wrinkles in clinical trials. An effect on elastin biosynthesis and elastic tissue accumulation in skin biopsies was observed in 21 female patients with photoaged facial skin, as measured at baseline and at 6 weeks of treatment. Histopathological evaluation revealed evidence of elastic fibre regeneration, including those extending perpendicularly towards the dermo‐epidermal junction within the papillary dermis. Elastin biosynthesis, measured by semi‐quantitative immunofluorescence with an antibody recognizing only the newly synthesized, uncrosslinked tropoelastin molecules, suggested statistically significant enhancement of elastin biosynthesis by the bi‐metal compound when applied twice daily. Accumulation of elastic fibres was confirmed by assay of desmosine, an elastin‐specific crosslink compound. These results suggest that the bi‐metal, 0.1% copper–zinc malonate‐containing cream has the propensity to increase elastin synthesis in human skin in vivo, and that regeneration of elastic fibres may contribute to wrinkle effacement in female patients with photoaged facial skin.