Non-coding RNAs as skin disease biomarkers, molecular signatures, and therapeutic targets.

Non-coding RNAs (ncRNAs) are emerging as biomarkers, molecular signatures, and therapeutic tools and targets for diseases. In this review, we focus specifically on skin diseases to highlight how two classes of ncRNAs-microRNAs and long noncoding RNAs-are being used to diagnose medical conditions of unclear etiology, improve our ability to guide treatment response, and predict disease prognosis. Furthermore, we explore how ncRNAs are being used as both as drug targets and associated therapies have unique benefits, risks, and challenges to development, but offer a distinctive promise for improving patient care and outcomes.

Commensal Cutibacterium acnes induce epidermal lipid synthesis important for skin barrier function.

Lipid synthesis is necessary for formation of epithelial barriers and homeostasis with external microbes. An analysis of the response of human keratinocytes to several different commensal bacteria on the skin revealed that Cutibacterium acnes induced a large increase in essential lipids including triglycerides, ceramides, cholesterol, and free fatty acids. A similar response occurred in mouse epidermis and in human skin affected with acne. Further analysis showed that this increase in lipids was mediated by short-chain fatty acids produced by Cutibacterium acnes and was dependent on increased expression of several lipid synthesis genes including glycerol-3-phosphate-acyltransferase-3. Inhibition or RNA silencing of peroxisome proliferator-activated receptor-α (PPARα), but not PPARß and PPARγ, blocked this response. The increase in keratinocyte lipid content improved innate barrier functions including antimicrobial activity, paracellular diffusion, and transepidermal water loss. These results reveal that metabolites from a common commensal bacterium have a previously unappreciated influence on the composition of epidermal lipids.