Biomechanical forces promote blood development through prostaglandin E2 and the cAMP-PKA signaling axis.
Biomechanical forces promote blood development through prostaglandin E2 and the cAMP-PKA signaling axis.
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DOI：
10.1084/jem.20142235
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发表时间：
2015-05-04
期刊：
影响因子：
--
通讯作者：
Wenzel PL
中科院分区：
文献类型：
--
作者：
Diaz MF;Li N;Lee HJ;Adamo L;Evans SM;Willey HE;Arora N;Torisawa YS;Vickers DA;Morris SA;Naveiras O;Murthy SK;Ingber DE;Daley GQ;García-Cardeña G;Wenzel PL
迪亚兹等人。研究表明，血流诱导的生化力通过诱导前列腺素 E2 和参与造血的信号通路，促进胚胎早期造血细胞的发育。血流促进发育中胚胎中最终造血干细胞（HSC）的出现，但影响造血潜力的血流动力学产生的信号仍不清楚。在这里，我们表明，流体剪切应力赋予了胚胎第 9.5 天早期造血组织的长期多谱系植入潜力，该胚胎阶段此前并未被描述为含有 HSC。对造血功能的影响部分是由壁剪切应力的级联下游介导的，涉及钙流出和前列腺素 E2 (PGE2)-环磷酸腺苷 (cAMP)-蛋白激酶 A (PKA) 信号轴的刺激。阻断主动脉-性腺-中肾 (AGM) 中的 PGE2-cAMP-PKA 通路可消除造血活性的增强。此外，Ncx1 心跳突变体以及 AGM 的静态培养物表现出较低水平的前列腺素合酶表达和 cAMP 反应元件结合蛋白 (CREB) 的磷酸化降低。与流暴露培养物类似，用合成类似物 16,16-二甲基-PGE2 短暂处理 AGM 可刺激成年受体的更牢固的植入和更大的淋巴重建。这些数据提供了一种由血流引起的生物力学力调节造血潜力的机制。
Diaz et al. show that biochemical forces induced by blood flow promote the development of hematopoietic cells at early embryonic stages via induction of prostaglandin E2 and signaling pathways involved in hematopoiesis. Blood flow promotes emergence of definitive hematopoietic stem cells (HSCs) in the developing embryo, yet the signals generated by hemodynamic forces that influence hematopoietic potential remain poorly defined. Here we show that fluid shear stress endows long-term multilineage engraftment potential upon early hematopoietic tissues at embryonic day 9.5, an embryonic stage not previously described to harbor HSCs. Effects on hematopoiesis are mediated in part by a cascade downstream of wall shear stress that involves calcium efflux and stimulation of the prostaglandin E2 (PGE2)–cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA) signaling axis. Blockade of the PGE2–cAMP–PKA pathway in the aorta-gonad-mesonephros (AGM) abolished enhancement in hematopoietic activity. Furthermore, Ncx1 heartbeat mutants, as well as static cultures of AGM, exhibit lower levels of expression of prostaglandin synthases and reduced phosphorylation of the cAMP response element–binding protein (CREB). Similar to flow-exposed cultures, transient treatment of AGM with the synthetic analogue 16,16-dimethyl-PGE2 stimulates more robust engraftment of adult recipients and greater lymphoid reconstitution. These data provide one mechanism by which biomechanical forces induced by blood flow modulate hematopoietic potential.
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影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
DOI：
10.1006/bbrc.1996.1104
发表时间：
1996-07-25
影响因子：
3.1
作者：
Alshihabi, SN;Chang, YS;Tarbell, JM
通讯作者：
Tarbell, JM
影响因子：
9.2
作者：
Iida, Atsuo;Sakaguchi, Kazuya;Sehara-Fujisawa, Atsuko
通讯作者：
Sehara-Fujisawa, Atsuko
DOI：
10.1073/pnas.88.24.11550
发表时间：
1991-12-01
影响因子：
11.1
作者：
HARDY, RR;HAYAKAWA, K
通讯作者：
HAYAKAWA, K
DOI：
10.1073/pnas.0704747104
发表时间：
2007-09-25
影响因子：
11.1
作者：
Nemeth, Michael J.;Topol, Lilia;Bodine, David M.
通讯作者：
Bodine, David M.