2063-LB: Transgenic Erythropoietin Overexpression Inhibits Dermal Fat Formation and HIF1a in the Skin and Causes Telogen Effluvium in Mouse Pups during the First Hair Cycle

Erythropoietin (EPO) plays an important role in promoting red blood cell production. In non-erythroid tissue, the EPO:EPO receptor (EPOR) interaction might affect fat synthesis and catabolism. Mice with deletion of EPOR in non-erythroid tissue become obese while transgenic mice overexpressing human EPO (Tg6) exhibit reduced body weight and fat mass compared with wild-type controls. How EPO:EPOR affects the synthesis and breakdown of dermal fat in skin, thereby affecting hair growth, is unknown. We verified EPOR expression in the dermal fat by fluorescent staining of skin tissue of EPOR-TdTomato-cre mice. We observed that EPOR knockout in HF stem cells did not affect skin hair growth nor showed significant differences in body weight and fat mass. In contrast, HF development in Tg6 mice was disrupted during the first catagen phase, resulting in formation of epithelium-lined HF cysts, filled with disorganized cysts. Transgenic human EPO in skin tissue was significantly higher than murine EPO during the first degenerative phase of HF development in Tg6 mice. The concomitant decrease in BODIPY positive cells suggested that high expression of transgenic EPO may affect hair growth during the first catagen phase by modulating lipogenesis and lipolysis of dermal fat. We assessed expression of transcription factors associated with EPO expression, HIF1aby Q-PCR. Indeed, increased EPO was accompanied by an increase in HIF1a. We found that EPO overexpression affected lipogenesis and lipolysis of dermal fat and HIF1a expression, disrupted hair growth during the first catagen phase and led to the formation of epithelial-lined HF cysts filled with disorganized keratin that ultimately manifest as truncal alopecia. In summary, we show here for the first time that EPO-HIF1a is essential in hair growth for the normal development and homeostasis of HFs.