RESUMEN
The uc.291 transcript controls keratinocytes differentiation by physical interaction with ACTL6A and subsequent induction of transcription of the genes belonging to the epidermal differentiation complex (EDC). Uc.291 is also implicated in the dedifferentiation phenotype seen in poorly differentiated cutaneous squamous cell carcinomas. Here, we would like to investigate the contribution of uc.291 to the unbalanced differentiation state of keratinocytes observed in hyperproliferative skin disorders, e. g., psoriasis. Psoriasis is a multifactorial inflammatory disease, caused by alteration of keratinocytes homeostasis. The imbalanced differentiation state, triggered by the infiltration of immune cells, represents one of the events responsible for this pathology. In the present work, we explore the role of uc.291 and its interactor ACTL6A in psoriasis skin, using quantitative real-time PCR (RT-qPCR), immunohistochemistry and bioinformatic analysis of publicly available datasets. Our data suggest that the expression of the uc.291 and of EDC genes loricrin and filaggrin (LOR, FLG) is reduced in lesional skin compared to nonlesional skin of psoriatic patients; conversely, the mRNA and protein level of ACTL6A are up-regulated. Furthermore, we provide evidence that the expression of uc.291, FLG and LOR is reduced, while ACTL6A mRNA is up-regulated, in an in vitro psoriasis-like model obtained by treating differentiated keratinocytes with interleukin 22 (IL-22). Furthermore, analysis of a publicly available dataset of human epidermal keratinocytes treated with IL-22 (GSE7216) confirmed our in vitro results. Taken together, our data reveal a novel role of uc.291 and its functional axis with ACTL6A in psoriasis disorder and a proof of concept that biological inhibition of this molecular axis could have a potential pharmacological effect against psoriasis and, in general, in skin diseases with a suppressed differentiation programme.
Asunto(s)
Psoriasis , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Piel/metabolismo , Piel/patología , Queratinocitos/metabolismo , Queratinocitos/patología , Psoriasis/genética , Psoriasis/metabolismo , ARN Mensajero/metabolismo , Actinas/metabolismo , Actinas/farmacología , Proteínas Cromosómicas no Histona/metabolismo , Proteínas de Unión al ADNRESUMEN
Although the gender gap has dramatically narrowed in recent decades, women remain underrepresented in many science, technology, engineering, and mathematics (STEM) fields. This study examined social and personal factors in relation to adolescent girls' motivation in STEM (math/science) versus non-STEM (English) subjects. An ethnically diverse sample of 579 girls ages 13-18 years (M = 15) in the U.S. completed questionnaires measuring their academic achievement, ability beliefs, values, and experiences. Social and personal factors were hypothesized to predict motivation (expectancy-value) differently in math/science (M/S) and English. Social factors included perceived M/S and English support from parents and peers. Personal factors included facets of gender identity (felt conformity pressure, gender typicality, gender-role contentedness), gender-related attitudes, and exposure to feminism. In addition, grades, age, parents' education, and ethnicity were controlled. Girls' M/S motivation was positively associated with mother M/S support, peer M/S support, gender-egalitarian beliefs, and exposure to feminism; it was negatively related to peer English support. Girls' English motivation was positively associated with peer English support as well as felt pressure from parents; it was negatively related to peer M/S support and felt peer pressure. The findings suggest that social and personal factors may influence girls' motivation in domain-specific ways.