Pituitary adenylate cyclase-activating polypeptide (PACAP) contributes to the proliferation of hematopoietic progenitor cells in murine bone marrow via PACAP-specific receptor.
Pituitary adenylate cyclase-activating polypeptide (PACAP) contributes to the proliferation of hematopoietic progenitor cells in murine bone marrow via PACAP-specific receptor.
复制标题
DOI：
10.1038/srep22373
复制
发表时间：
2016-02-29
影响因子：
4.6
通讯作者：
Shioda S
中科院分区：
文献类型：
--
作者：
Xu Z;Ohtaki H;Watanabe J;Miyamoto K;Murai N;Sasaki S;Matsumoto M;Hashimoto H;Hiraizumi Y;Numazawa S;Shioda S
腺苷酸环化酶激活多肽（PACAP）由adcyap 1编码，在外胚层发育过程中起重要作用。然而，PACAP在其他胚层发育中的作用尚不清楚。本研究评估了小鼠骨髓（BM）中PACAP特异性受体（PAC 1）基因和蛋白的表达。PAC 1+强表达的细胞体积大，核呈椭圆形，并与CD 34+细胞融合，表明前者是造血祖细胞（HPC）。与野生型小鼠相比，adcyap 1 −/−小鼠在细胞周期的S期表现出较低的多个潜在祖细胞群和细胞频率。在半固体培养中，外源性PACAP 38可显著增加粒/巨噬细胞祖细胞集落形成单位（CFU-GM）的数量，并出现两个高峰。PACAP还增加cyclinD 1和Ki 67 mRNA的表达。这些增加分别被PACAP受体拮抗剂PACAP 6 -38和VIP 6 -28完全和部分抑制。adcyap 1在BM中很少或没有表达，并且在adcyap 1 −/−和野生型小鼠中CFU-GM集落的数量相似。然而，PACAP的mRNA和蛋白质表达在椎旁交感神经节，支配胫骨BM，和BM腔的交感纤维。这些结果表明，交感神经支配可能是负责PACAP调节骨髓造血，主要是通过PAC 1。
Pituitary adenylate cyclase-activating polypeptide (PACAP, encoded by adcyap1) plays an important role in ectodermal development. However, the involvement of PACAP in the development of other germ layers is still unclear. This study assessed the expression of a PACAP-specific receptor (PAC1) gene and protein in mouse bone marrow (BM). Cells strongly expressing PAC1+ were large in size, had oval nuclei, and merged with CD34+ cells, suggesting that the former were hematopoietic progenitor cells (HPCs). Compared with wild-type mice, adcyap1−/− mice exhibited lower multiple potential progenitor cell populations and cell frequency in the S-phase of the cell cycle. Exogenous PACAP38 significantly increased the numbers of colony forming unit-granulocyte/macrophage progenitor cells (CFU-GM) with two peaks in semi-solid culture. PACAP also increased the expression of cyclinD1 and Ki67 mRNAs. These increases were completely and partially inhibited by the PACAP receptor antagonists, PACAP6-38 and VIP6-28, respectively. Little or no adcyap1 was expressed in BM and the number of CFU-GM colonies was similar in adcyap1−/− and wild-type mice. However, PACAP mRNA and protein were expressed in paravertebral sympathetic ganglia, which innervate tibial BM, and in the sympathetic fibers of BM cavity. These results suggested that sympathetic nerve innervation may be responsible for PACAP-regulated hematopoiesis in BM, mainly via PAC1.