Gonadal ER\u3b1/\u3b2, AR and TRPV1 gene expression: modulation by pain and morphine treatment in male and female rats.

The results of several studies strongly indicate a bidirectional relationship among gonadal hormones and pain. While gonadal hormones play a key role in pain modulation, they have been found to be affected by pain therapies in different experimental and clinical conditions. However, the effects of pain and pain therapy on the gonads are still not clear. In this study, we determined the long-lasting (72 h) effects of inflammatory pain (formalin test) and/or morphine on estrogen receptor (ER), androgen receptor (AR) and TRPV1 gene expression in the rat testis and ovary. The animals were divided into groups: animals receiving no treatment, animals exposed only to the experimental procedure (control group), animals receiving no pain but morphine (sham/morphine), animals receiving pain and morphine (formalin/morphine), and animals receiving only formalin (formalin/saline). Testosterone (T) and estradiol (E) were determined in the plasma at the end of the testing. In the sham/morphine rats, there were increases of ER\u3b1, ER\u3b2, AR and TRPV1 mRNA expression in the ovary; in the testis, ER\u3b1 and ER\u3b2 mRNA expression were reduced while AR and TRPV1 expression were unaffected by treatment. T and E plasma levels were increased in morphine-treated female rats, while T levels were greatly reduced in morphine-treated and formalin-treated males. In conclusion, both testicular and ovarian ER (ER\u3b1 and ER\u3b2) and ovarian AR and TRPV1 gene expression appear to be affected by morphine treatment, suggesting long-lasting interactions among opioids and gonads

SVEP1 plays a crucial role in epidermal differentiation.

SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell-cell adhesion in an integrin-dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT-PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three-dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1-specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell-cell adhesion with disadhesion between cells in Svep1-deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation. Exp Dermatol 2017 May; 26(5):423-430

Novel nonsense variants in SLURP1 and DSG1 cause palmoplantar keratoderma in Pakistani families

Inherited palmoplantar keratodermas (PPKs) are clinically and genetically heterogeneous and phenotypically diverse group of genodermatoses characterized by hyperkeratosis of the palms and soles. More than 20 genes have been reported to be associated with PPKs including desmoglein 1 (DSG1) a key molecular component for epidermal adhesion and differentiation. Mal de Meleda (MDM) is a rare inherited autosomal recessive genodermatosis characterized by transgrediens PPK, associated with mutations in the secreted LY6/PLAUR domain containing 1 (SLURP1) gene.This article is freely available online via Open Access. Click on the Publisher URL to access the full-text via the publisher's site