Sun Zhenjiang, Wang Benfang, Shen Ying, Ma Kunpeng, Wang Ting, Wang Yiqiang, Lin Dandan
Institute of Blood and Marrow Transplantation, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou Medical College, Soochow University, Suzhou 215006, China.
Department of Clinical Laboratory, The Affiliated Jiangyin Hospital of Southeast University, Jiangyin 214400, China.
Blood Sci. 2023 Jul 5;5(3):160-169. doi: 10.1097/BS9.0000000000000167. eCollection 2023 Jul.
Matrix remodeling is a critical process in hematopoiesis. The biology of MXRA7, as a matrix remodeling associated gene, has still not been reported in hematopoietic process. Public databases showed that MXRA7 expressed in hematopoietic stem cells, suggesting that it may be involved in hematopoiesis. We found that the amounts of megakaryocytes were lower in bone marrow and spleen from mice compared with that from wild-type mice. Knock-out of MXRA7 also reduced the amount of platelet in peripheral blood and affected the function of platelets. Knock-out of MXRA7 inhibited hematopoietic stem/progenitor cells differentiate to megakaryocytes possibly through down-regulating the expression of and . Moreover, knockdown of MXRA7 in MEG-01 cells could inhibit the cell proliferation and cell apoptosis. Knockdown of MXRA7 inhibited the differentiation of MEG-01 cells and proplatelet formation through suppressing the ERK/MAPK signaling pathway and the expression of β-tubulin. In conclusion, the current study demonstrated the potential significance of MXRA7 in megakaryocyte differentiation and platelet production. The novel findings proposed a new target for the treatment of platelet-related diseases, and much more investigations are guaranteed to dissect the mechanisms of MXRA7 in megakaryocyte differentiation and platelet production.
基质重塑是造血过程中的一个关键过程。作为一种与基质重塑相关的基因，MXRA7在造血过程中的生物学特性尚未见报道。公共数据库显示MXRA7在造血干细胞中表达，提示其可能参与造血过程。我们发现，与野生型小鼠相比，基因敲除MXRA7的小鼠骨髓和脾脏中的巨核细胞数量较少。敲除MXRA7还会减少外周血中血小板的数量，并影响血小板的功能。敲除MXRA7可能通过下调[具体基因1]和[具体基因2]的表达来抑制造血干/祖细胞向巨核细胞的分化。此外，在MEG-01细胞中敲低MXRA7可抑制细胞增殖和细胞凋亡。敲低MXRA7通过抑制ERK/MAPK信号通路和β-微管蛋白的表达来抑制MEG-01细胞的分化和前血小板形成。总之，本研究证明了MXRA7在巨核细胞分化和血小板生成中的潜在意义。这些新发现为血小板相关疾病的治疗提出了一个新靶点，并且需要更多的研究来深入剖析MXRA7在巨核细胞分化和血小板生成中的机制。
