Ginger stimulates hematopoiesis via Bmp pathway in zebrafish.
Ginger stimulates hematopoiesis via Bmp pathway in zebrafish.
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DOI：
10.1371/journal.pone.0039327
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Leung T
中科院分区：
文献类型：
--
作者：
Ferri-Lagneau KF;Moshal KS;Grimes M;Zahora B;Lv L;Sang S;Leung T
贫血是一种红细胞数量减少的血液疾病。红细胞生成，即红细胞分化的过程，在人类、小鼠和斑马鱼中是保守的。唯一已知的可用于治疗病理性贫血的药物是促红细胞生成素及其生物衍生物。然而，促红细胞生成素疗法会引起不良副作用、成本高以及静脉或皮下注射，因此需要开发更具成本效益的非肽替代品。生姜（Zingiber officinale）在传统医学中被广泛使用；然而，迄今为止，还没有科学研究证明生姜刺激造血的潜力。在这里，我们利用 gata1:dsRed 转基因斑马鱼胚胎研究生姜提取物对体内造血的影响，并鉴定出其生物活性成分 10-姜酚。我们证实生姜和10-姜酚可促进红系细胞中gata1的表达，并增加造血祖细胞标记物cmyb和scl的表达。我们还通过使用视频显微镜量化背主动脉中循环红细胞的数量，证明生姜和 10-姜酚可以促进斑马鱼急性溶血性贫血的造血恢复。我们发现原肠胚形成过程中生姜和 10-姜酚处理会导致 bmp2b 和 bmp7a 及其下游效应子 gata2 和 eve1 表达增加。在后期，生姜和10-姜酚可以诱导尾部造血组织区域bmp2b/7a、cmyb、scl和lmo2表达。我们通过使用Bmp激活的Bmp I型受体激酶抑制剂dorsomorphin、LND193189和DMH1进一步证实Bmp/Smad通路介导生姜的这种促进造血作用。我们的研究为进一步评估生姜及其生物活性成分在造血过程中的分子机制并研究其对成人的影响奠定了坚实的基础。我们的研究结果将为未来研究生姜在哺乳动物造血过程中的作用以开发新型红细胞生成促进剂提供基础。
Anemia is a hematologic disorder with decreased number of erythrocytes. Erythropoiesis, the process by which red blood cells differentiate, are conserved in humans, mice and zebrafish. The only known agents available to treat pathological anemia are erythropoietin and its biologic derivatives. However, erythropoietin therapy elicits unwanted side-effects, high cost and intravenous or subcutaneous injection, warranting the development of a more cost effective and non-peptide alternative. Ginger (Zingiber officinale) has been widely used in traditional medicine; however, to date there is no scientific research documenting the potential of ginger to stimulate hematopoiesis. Here, we utilized gata1:dsRed transgenic zebrafish embryos to investigate the effect of ginger extract on hematopoiesis in vivo and we identified its bioactive component, 10-gingerol. We confirmed that ginger and 10-gingerol promote the expression of gata1 in erythroid cells and increase the expression of hematopoietic progenitor markers cmyb and scl. We also demonstrated that ginger and 10-gingerol can promote the hematopoietic recovery from acute hemolytic anemia in zebrafish, by quantifying the number of circulating erythroid cells in the dorsal aorta using video microscopy. We found that ginger and 10-gingerol treatment during gastrulation results in an increase of bmp2b and bmp7a expression, and their downstream effectors, gata2 and eve1. At later stages ginger and 10-gingerol can induce bmp2b/7a, cmyb, scl and lmo2 expression in the caudal hematopoietic tissue area. We further confirmed that Bmp/Smad pathway mediates this hematopoiesis promoting effect of ginger by using the Bmp-activated Bmp type I receptor kinase inhibitors dorsomorphin, LND193189 and DMH1. Our study provides a strong foundation to further evaluate the molecular mechanism of ginger and its bioactive components during hematopoiesis and to investigate their effects in adults. Our results will provide the basis for future research into the effect of ginger during mammalian hematopoiesis to develop novel erythropoiesis promoting agents.
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影响因子：
2.5
作者：
Collery, Ross F.;Link, Brian A.
通讯作者：
Link, Brian A.
影响因子：
2.7
作者：
Dooley, KA;Davidson, AJ;Zon, LI
通讯作者：
Zon, LI
骨形态发生蛋白调节人造血干细胞的发育程序。
DOI：
10.1084/jem.189.7.1139
发表时间：
1999-04-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bhatia M;Bonnet D;Wu D;Murdoch B;Wrana J;Gallacher L;Dick JE
通讯作者：
Dick JE
影响因子：
64.5
作者：
Lee, HX;Ambrosio, AL;De Robertis, EM
通讯作者：
De Robertis, EM
影响因子：
64.8
作者：
Boisset, Jean-Charles;van Cappellen, Wiggert;Robin, Catherine
通讯作者：
Robin, Catherine