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Fig. 4 | Stem Cell Research & Therapy

Fig. 4

From: MicroRNA-9 modified bone marrow-derived mesenchymal stem cells (BMSCs) repair severe acute pancreatitis (SAP) via inducing angiogenesis in rats

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. eg 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

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