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.