Blood:造血细胞高表达CXCL4促进MPN骨髓纤维化进展

2020-08-05 MedSci原创 MedSci原创

细胞因子CXCL4/血小板因子4(PF4)的空间差异性表达标志着纤维化的进展;造血细胞CXCL4缺乏可减轻MPN表型,减少基质细胞激活和骨髓纤维化。

原发性骨髓纤维化(PMF)是一种骨髓增生性肿瘤(MPN),可导致骨髓(BM)进行性纤维化。虽然已广泛研究了参与PMF发病机制的细胞突变,但通过造血-基质交联的驱动基质激活和纤维化的顺序事件仍未明确。

通过非偏倚方法并在MPN患者中进行了验证,研究人员明确了趋化因子CXCL4/血小板因子4(PF4)的空间差异性表达标志着纤维化的进展。

造血细胞CXCL4缺乏可改善MPN表型,减少基质细胞活化和BM纤维化,并可减少3种PMF小鼠模型的:1)巨核细胞促纤维化通路的激活;2)纤维化驱动细胞炎症;3)巨核细胞和基质细胞的JAK/STAT激活。

该研究表明,在MPN中,CXCL4高表达具有促纤维化效应,是特征性炎症的调节因子。因此,靶向CXCL4或可成为一种减轻PMF炎症的有效方法。

原始出处:

Helene Gleitz,et al. Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN. Blood. July 29,2020.

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    2020-08-07 俅侠
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    2020-08-06 ms3000000449926787

    学习了

    0

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