100 research outputs found
Adipose cell differentiation: evidence for a two-step process in the polyamine-dependent Ob1754 clonal line
Role of spermidine in the expression of late markers of adipose conversion Effects of growth hormone
Translational implications of Th17-skewed inflammation due to genetic deficiency of a cadherin stress sensor
Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions and multiple allergies, and isolated patient keratinocytes exhibit increased proallergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the 3 tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1â/â skin showed a delay in expression of adhesion/differentiation/ keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17âskewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1â/â mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of 2 Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth, and treatment with a targeted therapy significantly improved skin lesions in patients
The Social Position and Intellectual Identity of the Renaissance Mathematician-Physicist Giovanni Battista Benedetti: A Case Study in the Socio-Political History of Mechanics
Growth hormone regulation of the expression of differentiation-dependent genes in preadipocyte Ob1771 cells
Growth hormone stimulates c-fos gene expression by means of protein kinase C without increasing inositol lipid turnover.
Inhibition of adhesionâspecific genes by Solidago virgaurea extract causes loss of Candida albicans biofilm integrity
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