血小板生成素
祖细胞
川地34
骨髓
癌症研究
造血
血管生成
蛋白激酶B
生物
免疫学
干细胞
细胞生物学
信号转导
作者
Hui Chen,Yingying Jiao,Chao Lin,Wenxuan Fan,Lindi Li,Bo Li,Liang Li,Xiaoyuan Zeng,Zongpeng Li,Hongfa Wei,Yuming Zhang,Benjie Zhou,Chun Chen,Jieyu Ye,Mo Yang
摘要
Summary Bone marrow endothelial progenitor cells (BM EPCs) are crucial in supporting haematopoietic regeneration, while the BM EPCs of haematological patients with chemotherapy‐induced thrombocytopenia (CIT) are unavoidably damaged. Therefore, the present study aimed to examine the effect of thrombopoietin (TPO) on the recovery of BM EPCs of CIT patients and to identify the underlying mechanisms. The cell functions were determined by 1,1‘‐dioctadecyl‐3,3,3’,3‘‐tetramethylindocarbocyanine perchlorate (Dil)–acetylated low‐density lipoprotein (Dil‐Ac‐LDL) uptake and fluorescein isothiocyanate (FITC)‐labeled Ulex europaeus agglutinin‐I (FITC‐UEA‐I) binding assay, as well as proliferation, migration and tube formation experiments. Endothelial cells were transfected with METTL16 lentivirus, followed by methylated RNA immunoprecipitation sequencing. Zebrafish with vascular defect was used as the in vivo model. TPO significantly improved the quantity and functions of BM EPCs from CIT patients in vitro and restored the subintestinal vein area of zebrafish with vascular defect in vivo. Mechanically, TPO enhanced the BM EPC functions through Akt signal mediated by METTL16, which was downregulated in BM EPCs of CIT patients and involved in the regulation of endothelial functions. The present study demonstrates that TPO improves the recovery of BM EPCs from CIT patients with haematological malignancies via METTL16/Akt signalling, which provides new insights into the role of TPO in treating CIT in addition to direct megakaryopoiesis.
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