No abstract

Epidermal growth factor receptor (EGFR), which is overexpressed in psoriatic lesions, has been proven to contribute to the hyperproliferation of keratinocytes in psoriasis. Single nucleotide polymorphisms (SNPs) involved in miRNAs that can regulate the expression of EGFR could potentially influence the development of psoriasis. The present study investigated the association between a functional SNP of rs2910164 in miR-146a and the risk of psoriasis in the Chinese Han population. A total of 521 Han Chinese patients with psoriasis and 582 healthy controls were recruited in this study. The miR-146a rs2910164 SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Overall, a significantly increased risk of psoriasis was associated with the rs2910164 miR-146a CG and GG genotypes (adjusted OR, 1.38; 95% CI, 1.06–1.80). Furthermore, the rs2910164G allele in miR-146a attenuated its inhibitory regulation on the expression of EGFR as well as the proliferation of human keratinocytes, and lowered the level of miR-146a in the psoriatic lesions. These findings indicate that the rs2910164G allele in miR-146a weakens its suppression on the proliferation of keratinocytes probably through the decreased inhibition of the target gene, EGFR, which may account for the increased risk of psoriasis in this study population.

Background Port-wine stain (PWS) is a congenital, progressive vascular malformation but the pathogenesis remains incompletely understood. Objective We sought to investigate the activation status of various kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT, phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide phospholipase C γ subunit, in PWS biopsy tissues. Methods Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients with PWS. Results c-Jun N-terminal kinase, extracellular signal-regulated kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was found in many adult hypertrophic PWS blood vessels but not in infants. Phosphoinositide phospholipase C γ subunit showed strong activation in nodular PWS blood vessels. Limitation Infantile PWS sample size was small. Conclusion Our data suggest a subsequent activation profile of various kinases during different stages of PWS: (1) c-Jun N-terminal and extracellular signal-regulated kinases are firstly and consecutively activated in all PWS tissues, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are involved in the hypertrophic development of PWS blood vessels; and (3) phosphoinositide phospholipase C γ subunit is activated in the most advanced stage of PWS and may participate in nodular formation.