Langerhans cells and SFRP2/Wnt/beta-catenin signalling control adaptation of skin epidermis to mechanical stretching.

Skin can be mechanically stimulated to grow through a clinical procedure called tissue expansion (TE). Using a porcine TE model, we determined that expansion promptly activates transcription of SFRP2 in skin and we revealed that in the epidermis, this protein is secreted by Langerhans cells (LCs). Similar to well-known mechanosensitive genes, the increase in SFRP2 expression was proportional to the magnitude of tension, showing a spike at the apex of the expanded skin.

Metabolic profiling and the metabolome-wide association study: significance level for biomarker identification.

High throughput metabolic profiling via the metabolome-wide association study (MWAS) is a powerful new approach to identify biomarkers of disease risk, but there are methodological challenges: high dimensionality, high level of collinearity, the existence of peak overlap within metabolic spectral data, multiple testing, and selection of a suitable significance threshold. We define the metabolome-wide significance level (MWSL) as the threshold required to control the family wise error rate through a permutation approach. We used 1H NMR spectroscopic profiles of 24 h urinary collections from the INTERMAP study.