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

Enik Bod, Arno Kromminga, Wolfgang Funk, Magdalena Laugsch, Ute Duske, Wolfgang Jelkmann, and Ralf Paus

Erythropoietin primarily serves as an essential growth factorfor erythrocyte precursor cells. However, there is increasingevidence that erythropoietin (EPO)/EPO receptor (EPO-R) signalingoperates as a potential tissue-protective system outside thebone marrow. Arguing that growing hair follicles (HF) are amongthe most rapidly proliferating tissues, we have here exploredwhether human HFs are sources of EPO and targets of EPO-R-mediatedsignaling. Human scalp skin and microdissected HFs were assessedfor EPO and EPO-R expression, and the effects of EPO on organ-culturedHFs were assessed in the presence/absence of a classical apoptosis-inducingchemotherapeutic agent. Here, we show that human scalp HFs expressEPO on the mRNA and protein level in situ, up-regulate EPO transcriptionunder hypoxic conditions, and express transcripts for EPO-Rand the EPO-stimulatory transcriptional cofactor hypoxia-induciblefactor-1. Although EPO does not significantly alter human hairgrowth in vitro, it significantly down-regulates chemotherapy-inducedintrafollicular apoptosis and changes the gene expression programof the HFs. The current study points to intriguing targets ofEPO beyond the erythropoietic system: human HFs are an extrarenalsite of EPO production and an extrahematopoietic site of EPO-Rexpression. They may recruit EPO/EPO-R signaling e.g., for modulatingHF apoptosis under conditions of hypoxia and chemotherapy-inducedstress.--Bodó, E., Kromminga, A., Funk, W., Laugsch,M, Duske, U., Jelkmann, W., Paus, R. Human hair follicles arean extrarenal source and a non-hematopoietic target of erythropoietin.