Blood：磷脂酰肌醇转运蛋白参与调控巨核细胞TGF-β1分泌和造血作用

2018-07-25 MedSci MedSci原创

中心点：磷脂酰肌醇转运蛋白（Pitps）可刺激巨核细胞分泌TGF-β1，进而调控造血。Pitpα-/-·β-/-巨核细胞的α颗粒的形态和功能均存在缺陷。摘要：Maegan Capitano等人推测磷脂酰肌醇转运蛋白（Pitp）介导的巨核细胞（MK）磷酸肌醇信号参与造血干细胞（HSC）和造血祖细胞（HPC）调控，故建立特异性敲除MKs和血小板的Pitps的小鼠模型（pitpα-/-和pitpα-/-

中心点：

磷脂酰肌醇转运蛋白（Pitps）可刺激巨核细胞分泌TGF-β1，进而调控造血。

Pitpα-/-·β-/-巨核细胞的α颗粒的形态和功能均存在缺陷。

摘要：

Maegan Capitano等人推测磷脂酰肌醇转运蛋白（Pitp）介导的巨核细胞（MK）磷酸肌醇信号参与造血干细胞（HSC）和造血祖细胞（HPC）调控，故建立特异性敲除MKs和血小板的Pitps的小鼠模型（pitpα-/-和pitpα-/-·β-/-），对此开展研究。

pitpα-/-和pitpα-/-·β-/-小鼠骨髓（BM）中的HSC、巨核系-红系祖细胞和HPC数量均减少。竞争性移植和限制性稀释分析显示pitpα-/-·β-/-BM的移植能力明显降低。与WT BM MK相比，培养pitpα-/-和pitpα-/-·β-/-BM MKs的培养基（CM）中含有更高水平的转化生长因子β1（TGF-β1）和白介素（IL）-4。pitpα-/-和pitpα-/-·β-/-MKs的CM可显着抑制HPC的克隆形成；在体外，该抑制作用可被中和性抗TGF-β抗体完全抵消；抗TGF-β抗体治疗pitpα-/-·β-/-小鼠也可完全逆转其BM HSC和HPC数量缺陷。在体外，TGF-β和IL-4可协同抑制HPC克隆形成。pitpα-/-·β-/-MKs的电子显微镜分析其超微结构发现α颗粒缺乏，还存在大的畸形的多囊体。血管性血友病因子和血小板反应蛋白，类似于TGF-β，均储存于MKs的α颗粒，在培养pitpα-/-·β-/-MKs的CM中也表现为增高。

总而言之，敲除MKs的Pitps可通过扰乱α颗粒的正常生理、破坏TGF-β分泌间接影响造血作用。

原始出处：

Maegan Capitano，et al. Phosphatidylinositol transfer proteins regulate megakaryocyte TGF-β1 secretion and hematopoiesis in mice. Blood 2018 ：blood-2017-09-806257； doi： https：//doi.org/10.1182/blood-2017-09-806257

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2018-11-01 chentianping

#TGF-β1#

62 0
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2019-06-28 yzh409

#转运#

104 0
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2019-06-29 changhe713

#TGF#

74 0
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2018-08-15 gwc392

#分泌#

65 0
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2019-01-14 zhouqu_8

#磷脂酰肌醇转运蛋白#

0 0
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2018-07-27 ms6980045490879608

#TGF-β#

65 0
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2018-07-27 liuquan

#巨核细胞#

113 0
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2018-07-27 俅侠

#造血#

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