Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin

Erythropoietin primarily serves as an essential growth factor for erythrocyte precursor cells. However, there is increasing evidence that erythropoietin ( EPO)/EPO receptor ( EPO-R) signaling operates as a potential tissue-protective system outside the bone marrow. Arguing that growing hair follicles ( HF) are among the most rapidly proliferating tissues, we have here explored whether human HFs are sources of EPO and targets of EPO-R-mediated signaling. Human scalp skin and microdissected HFs were assessed for EPO and EPO-R expression, and the effects of EPO on organ-cultured HFs were assessed in the presence/absence of a classical apoptosis-inducing chemotherapeutic agent. Here, we show that human scalp HFs express EPO on the mRNA and protein level in situ, up-regulate EPO transcription under hypoxic conditions, and express transcripts for EPO-R and the EPO-stimulatory transcriptional cofactor hypoxia-inducible factor-1 alpha. Although EPO does not significantly alter human hair growth in vitro, it significantly down-regulates chemotherapy-induced intrafollicular apoptosis and changes the gene expression program of the HFs. The current study points to intriguing targets of EPO beyond the erythropoietic system: human HFs are an extrarenal site of EPO production and an extrahematopoietic site of EPO-R expression. They may recruit EPO/EPO-R signaling e. g., for modulating HF apoptosis under conditions of hypoxia and chemotherapy-induced stress. - Bodo, E., Kromminga, A., Funk, W., Laugsch, M, Duske, U., Jelkmann, W., Paus, R. Human hair follicles are an extrarenal source and a non-hematopoietic target of erythropoietin.