Alain Hovnanian

..The identification of novel processed forms of LEKTI provides the basis for future functional and structural studies of fragments with physiological relevance...

..Although the precise disease mechanisms remain to be understood, these discoveries open a new field in research for the understanding and the treatment of these distressing disorders...

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..These results should allow for early prenatal diagnosis of HI and lend hope to the possibility of a specific treatment for this devastating disorder...

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..6). This is the first example of a modifier gene in RDEB and has implications for its prognosis and possible new treatments...

..Using this gene as an example, we describe general methods that demonstrate the feasibility and efficacy of the antisense-mediated exon-skipping strategy to reframe transcripts...

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..These include skin barrier impairment, mechanical stress secondary to stratum corneum detachment, as well as protease-induced proinflammatory and proallergic pathways, including PAR2-mediated overexpression of TSLP...

..These results highlight the importance of the control of epidermal protease activity in skin homeostasis and designate ELA2 as a major protease driving the pathogenesis of NS...

..Keratinocytes thus are unique among mammalian cells in their ability to use the Golgi Ca2+ store to mediate Ca2+ signaling...

..This new founder mutation, the most frequent mutation described in European populations so far, and these unusual intronic mutations, widen the clinical and molecular spectrum of NS and offer new diagnostic perspectives for NS patients...

..This article is part of a Special Issue entitled: 11th European Symposium on Calcium...

..They disclose a new mechanism of skin homeostasis by which the epidermal pH gradient allows precisely regulated KLK5 activity and corneodesmosomal cleavage in the most superficial layers of the stratum corneum...

..This is consistent with the diagnosis of the moderately severe form of RDEB in the proband, at variance with the most severe form, RDEB Hallopeau-Siemens, that would arise from complete collagen VII deficiency...

..Our data indicate that mouse Spink5/Lekti, like its human counterpart, is involved in the control of epithelial tissue homeostasis, but also highlight specific features of the murine gene and protein...

..This led to the detection of three large ABCC6 deletions, and two deletions of a single exon (exon 1 and exon 21). Thus QMPSF identified the causative mutation in 28% (5/18) of the uncharacterized ABCC6 mutant alleles in this cohort...

..M119T mutation still suffered from severe EBS-DM, whereas the patient harboring the c.1246delC mutation has improved over time. These cases illustrate genotype-phenotype correlations and have implications for genetic counselling of EBS...

..We review recent work into the function of these pumps in human keratinocytes and discuss how mutations in these genes might cause these diseases by altering the formation or stability of desmosomes...

..We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD...

..This report provides evidence for residual ABCA12 expression in HI, and demonstrates the efficiency of early DNA-based PD of HI...

..We also demonstrate an interaction between SERCA2 and desmoplakin during differentiation. Our results provide further insights into the critical role of calcium ATPases in maintaining epidermal integrity...

..This finding indicates that SERCA2b plays a key role in the biology of the epidermis, and its defects are sufficient to cause Darier's disease...

..This result demonstrates loss of function of the sarco(endo)plasmic reticulum Ca2+ ATPase2 mutant in acrokeratosis verruciformis, thus providing evidence that acrokeratosis verruciformis and Darier's disease are allelic disorders...

..In this case, the disease may be a consequence of the low expression level and/or reduction of Ca2+ affinity and sensitivity to inhibition by lumenal Ca2+...

..Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3...

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..These findings confirm the role of cathelicidin in skin inflammatory responses and suggest an explanation for the pathogenesis of rosacea by demonstrating that an exacerbated innate immune response can reproduce elements of this disease...

..Protocols to select for stable integrants and to assess the integration event(s) within the keratinocyte genome will also be provided...

..This work further supports the implication of premature corneodesmosomal cadherin degradation in the pathogenesis of NS and provides evidence for additional factors playing a role in disease expression...

..Our data provide new insights into the biological functions of LG and the pathogenesis of NS...

..These data demonstrate a "proof of principle" for genomic DNA vectors as a means of restoring collagen VII production in RDEB-HS skin and help develop future gene therapy protocols...