Fig. 4

miR-9, released from BMSCs into VECs, can target the VE-cadherin gene and induce the expression of angiogenic genes in VECs. a miR-9 in pancreatic tissues was downregulated in the PBS + SAP group compared with the NC group, whereas it was significantly upregulated by pri-miR-9-BMSCs, compared with SAP, SAP+PBS, BMSCs, EV-BMSCs, and TuD-BMSCs. Data are shown as the mean ± SD for at least three separate experiments. ^%p < 0.05, compared with NC, ^**p < 0.01, compared with NC, ^@@p < 0.01, compared with SAP, ^&&p < 0.01, compared with PBS treatment, ^#p < 0.05, compared with BMSCs, ^$p < 0.05, compared with EV-BMSCs, ⁺p < 0.05, compared with TuD-BMSCs by using two-tailed t test. b GFP-BMSCs could deliver exogenous Cy3-miR-9a-5p to the liver, spleen, lung, and pancreas, and the number was higher in the liver and spleen. c Eight paired base between miR-9 and VE-cadherin and the structure of the wild-type VE-cadherin 3′-UTR (wtUTR) or mutant VE-cadherin 3′-UTR (CAAAG→TCGCT) (mutUTR) were cloned into the psiCHECK-2 plasmid to produce the recombinant vectors, wtUTR psiCHECK-2 and mutUTR psiCHECK-2, harboring the predicted binding sites of miR-9. d The activity of firefly luciferase was significantly decreased by miR-9 and rescued by mutant of VE-cadherin 3′-UTR. e–g Co-culture of VECs and BMSCs transfected with cy3-miR-9 showed that BMSCs secreted cy3-miR-9 into VECs and inhibited the expression of VE-cadherin and β-catenin and upregulated Ang-1, CXCR4, TIE-2 and p-AKT. ^*p < 0.05, ^**p < 0.01, and ^***p < 0.001, compared with NC group, ^@p < 0.05, ^@@p < 0.01, and ^@@@p < 0.001, compared with miR-9 con by using paired t test. VECs, vascular endothelial cells; BMSCs, bone marrow-derived mesenchymal stem cells; GFP, green fluorescent protein; gPCR, general PCR; qRT-PCR, quantitative real-time PCR; SAP, severe acute pancreatitis; NC, normal control; miR-9 con, miR-9 mimic control