Olfactomedin-4 supports cutaneous wound healing by promoting skin cell proliferation and migration

Olfactomedin-4 (OLFM4) is an olfactomedin-domain containing glycoprotein that acts as an important regulator of cell adhesion, proliferation, gastrointestinal inflammation, innate immunity and cancer metastasis. In the present study we aimed to elucidate its role in skin regeneration and wound healing. We found that OLFM4 expression is transiently upregulated in the proliferative phase of cutaneous wound healing in humans as well as in mice. Moreover, a significant increase in OLFM4 expression was detected in the skin of lesional psoriasis, a disease characterized by keratinocyte hyperproliferation. In vitro experiments demonstrated that OLFM4 can selectively stimulate keratinocyte proliferation and increase both keratinocyte and fibroblast migration ability. Using proteotransciptomic pathway analysis we revealed that transcription factors POU5F1/OCT4 and ESR1 acted as hubs for OLFM4-dependent signalling in keratinocytes. Overall design: Changes in human primary skin keratinocyte and fibroblast RNA profiles in response to stimulation with recombinant OLFM4 protein