Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin
Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin
复制标题
DOI：
10.1096/fj.07-8628com
复制
发表时间：
2007-10-01
期刊：
影响因子：
4.8
通讯作者：
Paus, Ralf
中科院分区：
文献类型：
--
作者：
Bodo, Eniko;Kromminga, Arno;Paus, Ralf
促红细胞生成素主要用作红细胞前体细胞的必需生长因子。然而，有越来越多的证据表明，促红细胞生成素（EPO）/EPO受体（EPO-R）信号作为一个潜在的组织保护系统的骨髓外。认为生长中的毛囊（HF）是增殖最快的组织之一，我们在这里探讨了人类毛囊是否是EPO的来源和EPO-R介导的信号转导的靶点。评估人头皮皮肤和显微切割的HFs的EPO和EPO-R表达，并在存在/不存在经典的促凋亡诱导化疗剂的情况下评估EPO对器官培养的HFs的影响。在这里，我们表明，人类头皮HFs表达EPO的mRNA和蛋白质水平原位，在缺氧条件下上调EPO的转录，并表达EPO-R和EPO刺激转录辅因子缺氧诱导因子-1 α的转录本。虽然EPO在体外并不显著改变人毛发生长，但它显著下调化疗诱导的毛囊内细胞凋亡，并改变HFs的基因表达程序。目前的研究指出了红细胞生成系统以外EPO的有趣靶点：人HF是EPO产生的肾外位点和EPO-R表达的造血外位点。它们可以募集EPO/EPO-R信号通路。例如，在一个实施例中，用于在缺氧和化疗诱导的应激条件下调节HF细胞凋亡。- Bodo，E.，Kromminga，A.，Funk，W.，Laugsch，M，Duske，U.，Jelkmann，W.，保斯河人毛囊是红细胞生成素的肾外来源和非造血靶点。
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.