Recessive dystrophic epidermolysis bullosa ( RDEB ), Kindler syndrome ( KS ) and xeroderma pigmentosum complementation group C ( XPC ) are three cancer‐prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders.
To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB , KS and XPC .
We conducted RNA ‐Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies.
Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix ( ECM ) proteins. Western blot and immunofluorescence in situ analyses validated the RNA ‐Seq data. In addition, enzyme‐linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB .
Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury‐sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB , XPC and KS .
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13 Nov 2019
Find out how changing immunosuppressive treatment practices have impacted SCC and BCC cancer risk in organ transplant recipients at https://t.co/wlvY9C1BnB #SCC #BCC #organtransplant #epidemiology https://t.co/tofI5FYhdu
13 Nov 2019
RT The British Association of Dermatologists @HealthySkin4All: We are very excited to be planning the launch of a new open access journal, for which we are now looking for an Editor-in-Chief. Full details and information on how to apply for this role can be found here: https://t.co/42Fego0m99 @BrJDermatol @ced_wiley https://t.co/RAtLL76qpd
12 Nov 2019
Why has there been a significant reduction in the incidences of both SCC and BCC in organ transplant recipients over the past two decades? https://t.co/9LZepIh0V0 #SCC #BCC #organtransplant #epidemiology https://t.co/7mFJDPG3ch
12 Nov 2019
RT The British Association of Dermatologists @HealthySkin4All: There is a need for more economic studies which look at the costs and effectiveness of two or more eczema treatments. These types of studies help inform how healthcare resources are used. https://t.co/jXK2mF2WQe @BrJDermatol @Wiley_Health @eczemasociety https://t.co/r90pWBEcRK