miR-363-5p regulates endothelial cell properties and their communication with hematopoietic precursor cells

Journal of Hematology & Oncology

Sérgio Dias¹  Mário Ramirez¹  Francisco Pinto¹  Sandra I Aguiar¹  Joana Valente³  Francisco Caiado³  Ana L Gomes³  Catarina Osório²  Joana Afonso¹  Ana Costa³ 

[1] Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Edificio Egas Moniz, Av. Prof Egas Moniz, Lisbon 1649-028, Portugal;Cardiff School of Biosciences, Biomedical Sciences Building, Museum Avenue, Biomedical Sciences Building, Museum Avenue, Cardiff, UK;Neoangiogenesis Group, Instituto Gulbenkian de Ciência, Oeiras, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal

关键词: Cell interactions;    miRNA;    Hematopoietic progenitors;    Endothelial cell;    Bone marrow;   

Others  :  802541
DOI  :  10.1186/1756-8722-6-87

 received in 2013-11-06, accepted in 2013-11-15,  发布年份 2013

【 摘 要 】

Recent findings have shown that the blood vessels of different organs exert an active role in regulating organ function. In detail, the endothelium that aligns the vasculature of most organs is fundamental in maintaining organ homeostasis and in promoting organ recovery following injury. Mechanistically, endothelial cells (EC) of tissues such as the liver, lungs or the bone marrow (BM) have been shown to produce “angiocrine” factors that promote organ recovery and restore normal organ function. Controlled production of angiocrine factors following organ injury is therefore essential to promote organ regeneration and to restore organ function. However, the molecular mechanisms underlying the coordinated production and function of such “angiocrine” factors are largely undisclosed and were the subject of the present study. In detail, we identified for the first time a microRNA (miRNA) expressed by BM EC that regulates the expression of angiocrine genes involved in BM recovery following irradiation. Using a microarray-based approach, we identified several miRNA expressed by irradiated BMEC. After validating the variations in miRNA expression by semi-quantitative PCR, we chose to study further the ones showing consistent variations between experiments, and those predicted to regulate (directly or indirectly) angiogenic and angiocrine factors. Of the mi-RNA that were chosen, miR-363-5p (previously termed miR-363*) was subsequently shown to modulate the expression of numerous EC-specific genes including some angiocrine factors. By luciferase reporter assays, miR-363-5p is shown to regulate the expression of angiocrine factors tissue inhibitor of metalloproteinases-1 (Timp-1) and thrombospondin 3 (THBS3) at post-transcriptional level. Moreover, miR-363-5p reduction using anti-miR is shown to affect EC angiogenic properties (such as the response to angiogenic factors stimulation) and the interaction between EC and hematopoietic precursors (particularly relevant in a BM setting). miR-363-5p reduction resulted in a significant decrease in EC tube formation on matrigel, but increased hematopoietic precursor cells adhesion onto EC, a mechanism that is shown to involve kit ligand-mediated cell adhesion. Taken together, we have identified a miRNA induced by irradiation that regulates angiocrine factors expression on EC and as such modulates EC properties. Further studies on the importance of miR-363-5p on normal BM function and in disease are warranted.

【 授权许可】

   
2013 Costa et al.; licensee BioMed Central Ltd.

【 图 表 】

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