The RAR-RXR as well as the RXR-RXR pathway is involved in signaling growth inhibition of human CD34+ erythroid progenitor cells.
The RAR-RXR as well as the RXR-RXR pathway is involved in signaling growth inhibition of human CD34+ erythroid progenitor cells.
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RAR-RXR 以及 RXR-RXR 途径参与人 CD34 红系祖细胞的信号生长抑制。
作者：
L. Rusten;I. Dybedal;H. Blomhoff;R. Blomhoff;E. Smeland;S. Jacobsen
以前的研究表明，视黄酸（RA），类似于肿瘤坏死因子-α（TNF-α），可以作为骨髓祖细胞生长的双功能调节剂，因为它可以刺激粒细胞-巨噬细胞集落刺激因子（GM-CSF）或白细胞介素-3（IL-3）诱导的GM集落形成，但有效地抑制G-CSF诱导的生长。本研究使用高度富集的人CD 34+以及Lin-鼠骨髓祖细胞，证明了9-顺式-RA对爆发形成单位红系（BFU-E）集落形成的有效抑制作用，而与刺激生长的细胞因子无关。特别地，9-cis-RA有效地抑制BFU-E对促红细胞生成素（Epo）（100%）、干细胞因子（SCF）+ Epo（92%）、IL-3 + Epo（97%）、IL-4 + Epo（88%）和IL-9 + Epo（100%）的反应的生长。当CD 34+祖细胞以每孔一个细胞接种时，红系集落生长也受到抑制，表明RA的直接作用。使用选择性结合和激活RAR-RXR或RXR-RXR二聚体的视黄酸受体（RAR）和类维生素A X受体（RXR）的合成配体，我们分别剖析了两种类维生素A反应途径在正常骨髓和红系祖细胞生长调节中的参与。反式激活研究表明，RAR（Ro 13-7410）和RXR（Ro 25-6603和Ro 25-7386）配体在100 nmol/L时具有高度选择性。在该浓度下，Ro 13-7410可有效抑制G-CSF刺激的髓系细胞以及SCF + Epo诱导的红系细胞集落生长。在相同浓度下，Ro 25-6603和Ro 25-7386对G-CSF诱导的集落形成几乎没有影响，而它们分别抑制SCF + Epo刺激的BFU-E集落生长的75%和53%。因此，RAR-RXR反应途径可以发出正常骨髓髓系和红系祖细胞生长抑制的信号。此外，我们证明了RXR-RXR途径在介导红系祖细胞而非髓系祖细胞的生长抑制中的独特参与。
Previous studies have shown that retinoic acid (RA), similar to tumor necrosis factor-alpha (TNF-alpha), can act as a bifunctional regulator of the growth of bone marrow progenitors, in that it can stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF)- or interleukin-3 (IL-3)-induced GM colony formation, but potently inhibit G-CSF-induced growth. The present study, using highly enriched human CD34+ as well as Lin- murine bone marrow progenitor cells, demonstrates a potent inhibitory effect of 9-cis-RA on burst-forming unit-erythroid (BFU-E) colony formation regardless of the cytokine stimulating growth. Specifically, 9-cis-RA potently inhibited the growth of BFU-E response to erythropoietin (Epo) (100%), stem cell factor (SCF) + Epo (92%), IL-3 + Epo (97%), IL-4 + Epo (88%), and IL-9 + Epo (100%). Erythroid colony growth was also inhibited when CD34+ progenitors were seeded at one cell per well, suggesting a direct action of RA. Using synthetic ligands to retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that selectively bind and activate RAR-RXR or RXR-RXR dimers, respectively, we dissected the involvement of the two retinoid response pathways in the regulation of normal myeloid and erythroid progenitor cell growth. Transactivation studies showed that both the RAR (Ro 13-7410) and RXR (Ro 25-6603 and Ro 25-7386) ligands were highly selective at 100 nmol/L. At this concentration, Ro 13-7410 potently inhibited G-CSF-stimulated myeloid as well as SCF + Epo-induced erythroid colony growth. At the same concentration, Ro 25-6603 and Ro 25-7386 had little or no effect on G-CSF-induced colony formation, whereas they inhibited 75% and 53%, respectively, of SCF + Epo-stimulated BFU-E colony growth. Thus, the RAR-RXR response pathway can signal growth inhibition of normal bone marrow myeloid and erythroid progenitor cells. In addition, we demonstrate a unique involvement of the RXR-RXR pathway in mediating growth inhibition of erythroid but not myeloid progenitor cells.
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9-顺式视黄酸：对体外正常和白血病造血的影响。
影响因子：
20.3
作者：
Sakashita,A;Kizaki,M;Pakkala,S;Schiller,G;Tsuruoka,N;Tomosaki,R;Cameron,JF;Dawson,MI;Koeffler,HP
通讯作者：
Koeffler,HP
视黄酸处理的 HL-60 细胞中转化生长因子-β 1 (TGF-β 1)、受体表达和 TGF-β 1 蛋白产生的诱导：可能是 TGF-β 1 介导的自分泌抑制。
影响因子：
20.3
作者：
Falk,LA;DeBenedetti,F;Lohrey,N;Birchenall-Roberts,MC;Ellingsworth,LW;Faltynek,CR;Ruscetti,FW
通讯作者：
Ruscetti,FW
骨髓增生异常综合征中造血前体细胞对 13-顺式视黄酸和 1,25 二羟基维生素 D3 的反应。
影响因子：
20.3
作者：
Swanson,G;Picozzi,V;Morgan,R;Hecht,F;Greenberg,P
通讯作者：
Greenberg,P
DOI：
10.1172/jci111853
发表时间：
1985-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
S. W. Mamus;S. Beck-Schroeder;E. Zanjani
通讯作者：
S. W. Mamus;S. Beck-Schroeder;E. Zanjani
影响因子：
56.9
作者：
LEHMANN, JM;JONG, L;PFAHL, M
通讯作者：
PFAHL, M