Skin is made up of two main layers: the epidermis is the outer layer containing epithelial keratinocytes and the underlying dermis, made up of fibroblasts and other cells. Signals are exchanged between these layers to coordinate their function, but dissecting these signals is tricky. For example, PPARβ/δ is an important protein for maintaining healthy skin, but its precise function remains controversial. PPARβ/δ is a nuclear hormone receptor that plays important roles in diabetes, obesity and metabolic-associated illness.

“Fibroblasts often play important roles by communicating with epithelial cells. The exploration of the role of PPARb/d in the fibroblast biology in mice is hampered because currently it not possible to delete a gene exclusively from the dermis. We used organotypic skin culture to dissect these networks and to study how the different types of cells could communicate with each other,” says Tan.

Chong et al. discovered that PPARβ/δ in the fibroblasts has a homeostatic control of keratinocyte proliferation and differentiation by regulating IL-1 signaling. The authors found that PPARβ/δ stimulates the production of sIL-1ra, a protein that inhibits IL-1 signaling by competing for the IL-1 receptor. Normally, this would decrease the IL-1 signal received by fibroblasts and therefore reduce the growth factor signals sent back to the keratinocytes. But in PPARβ/δ's absence, fibroblasts keep stimulating keratinocyte division.

Pre-clinical studies are needed to realize the potential clinical applications of this work in wound healing. Currently, PPARb/d drugs for the treatment of various metabolic illnesses such as diabetes, are in trials are conducted by various pharmaceutical companies.