Limits...
MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.

Li Y, Mao L, Gao Y, Baral S, Zhou Y, Hu B - Sci Rep (2015)

Bottom Line: We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke.This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke.This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

ABSTRACT
Previous studies have suggested that microRNA-107 (miR-107) regulates cell migration in tumor and promotes Hypoxia Inducible Factor 1α (HIF1α) regulated angiogenesis under hypoxia. We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke. Such finding led us to hypothesize that miR-107 might regulate post-stroke angiogenesis and therefore serve as a therapeutic target. We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats. We demonstrated that miR-107 could directly down-regulate Dicer-1, a gene that encodes an enzyme essential for processing microRNA (miRNA) precursors. This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke. This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

No MeSH data available.


Related in: MedlinePlus

Increased miR-107 in IBZ promotes angiogenesis in rat after pMCAO.(A,B) qRT-PCR showed the expression of miR-107 was increased in the IBZ of rats subjected to pMCAO on 3rd and 7th day. *P < 0.05, vs. control group. (C) Capillary density was evaluated by FITC tail vein injection, and then the vessel number was quantified by FITC (green). (D) Quantification of capillary density. Data are presented as mean ± SD. Scale bar = 10 μm in D (applies to C). *P < 0.05, vs. antagomir-ctl. (E) qRT-PCR showed the expression of miR-107 after lateral cerebral ventricle injection of antagomir-107 on day 7 after pMCAO. *P < 0.05, vs. antagomir-ctl. (F) Exposure to OGD for 12 h increases miR-107 expression in RBMECs demonstrated by using qRT-PCR. (G) HUVECs. (H) Astrocytes. Data are presented as mean ± SD. *P < 0.05, vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4543985&req=5

f1: Increased miR-107 in IBZ promotes angiogenesis in rat after pMCAO.(A,B) qRT-PCR showed the expression of miR-107 was increased in the IBZ of rats subjected to pMCAO on 3rd and 7th day. *P < 0.05, vs. control group. (C) Capillary density was evaluated by FITC tail vein injection, and then the vessel number was quantified by FITC (green). (D) Quantification of capillary density. Data are presented as mean ± SD. Scale bar = 10 μm in D (applies to C). *P < 0.05, vs. antagomir-ctl. (E) qRT-PCR showed the expression of miR-107 after lateral cerebral ventricle injection of antagomir-107 on day 7 after pMCAO. *P < 0.05, vs. antagomir-ctl. (F) Exposure to OGD for 12 h increases miR-107 expression in RBMECs demonstrated by using qRT-PCR. (G) HUVECs. (H) Astrocytes. Data are presented as mean ± SD. *P < 0.05, vs. control group.

Mentions: The expression of miR-107 was up-regulated by 2.21 fold and 2.88 fold (Fig. 1A,B, P < 0.05) on day 3 and day 7 respectively in the IBZ of pMCAO rats compared to control as detected by quantitative real-time PCR (qRT-PCR). Quantitative evaluation showed that blockage of miR-107 by lateral ventricular injection of antagomir-107 in pMCAO rats (Fig. 1E, P < 0.05) resulted in reduction of number of capillaries in IBZ by 65.4% as compared with antagomir control group (antagomir-ctl) (Fig. 1C,D, P < 0.05). qRT-PCR showed that miR-107 level was upregulated significantly by 2.99 fold, 2.24 fold and 2.96 fold in rat brain microvascular endothelial cells (RBMECs), HUVECs and astrocytes respectively under Oxygen- Glucose Deprivation (OGD) compared with normoxia after 12 hours. (Fig. 1F–H, P < 0.05).


MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.

Li Y, Mao L, Gao Y, Baral S, Zhou Y, Hu B - Sci Rep (2015)

Increased miR-107 in IBZ promotes angiogenesis in rat after pMCAO.(A,B) qRT-PCR showed the expression of miR-107 was increased in the IBZ of rats subjected to pMCAO on 3rd and 7th day. *P < 0.05, vs. control group. (C) Capillary density was evaluated by FITC tail vein injection, and then the vessel number was quantified by FITC (green). (D) Quantification of capillary density. Data are presented as mean ± SD. Scale bar = 10 μm in D (applies to C). *P < 0.05, vs. antagomir-ctl. (E) qRT-PCR showed the expression of miR-107 after lateral cerebral ventricle injection of antagomir-107 on day 7 after pMCAO. *P < 0.05, vs. antagomir-ctl. (F) Exposure to OGD for 12 h increases miR-107 expression in RBMECs demonstrated by using qRT-PCR. (G) HUVECs. (H) Astrocytes. Data are presented as mean ± SD. *P < 0.05, vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543985&req=5

f1: Increased miR-107 in IBZ promotes angiogenesis in rat after pMCAO.(A,B) qRT-PCR showed the expression of miR-107 was increased in the IBZ of rats subjected to pMCAO on 3rd and 7th day. *P < 0.05, vs. control group. (C) Capillary density was evaluated by FITC tail vein injection, and then the vessel number was quantified by FITC (green). (D) Quantification of capillary density. Data are presented as mean ± SD. Scale bar = 10 μm in D (applies to C). *P < 0.05, vs. antagomir-ctl. (E) qRT-PCR showed the expression of miR-107 after lateral cerebral ventricle injection of antagomir-107 on day 7 after pMCAO. *P < 0.05, vs. antagomir-ctl. (F) Exposure to OGD for 12 h increases miR-107 expression in RBMECs demonstrated by using qRT-PCR. (G) HUVECs. (H) Astrocytes. Data are presented as mean ± SD. *P < 0.05, vs. control group.
Mentions: The expression of miR-107 was up-regulated by 2.21 fold and 2.88 fold (Fig. 1A,B, P < 0.05) on day 3 and day 7 respectively in the IBZ of pMCAO rats compared to control as detected by quantitative real-time PCR (qRT-PCR). Quantitative evaluation showed that blockage of miR-107 by lateral ventricular injection of antagomir-107 in pMCAO rats (Fig. 1E, P < 0.05) resulted in reduction of number of capillaries in IBZ by 65.4% as compared with antagomir control group (antagomir-ctl) (Fig. 1C,D, P < 0.05). qRT-PCR showed that miR-107 level was upregulated significantly by 2.99 fold, 2.24 fold and 2.96 fold in rat brain microvascular endothelial cells (RBMECs), HUVECs and astrocytes respectively under Oxygen- Glucose Deprivation (OGD) compared with normoxia after 12 hours. (Fig. 1F–H, P < 0.05).

Bottom Line: We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke.This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke.This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

ABSTRACT
Previous studies have suggested that microRNA-107 (miR-107) regulates cell migration in tumor and promotes Hypoxia Inducible Factor 1α (HIF1α) regulated angiogenesis under hypoxia. We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke. Such finding led us to hypothesize that miR-107 might regulate post-stroke angiogenesis and therefore serve as a therapeutic target. We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats. We demonstrated that miR-107 could directly down-regulate Dicer-1, a gene that encodes an enzyme essential for processing microRNA (miRNA) precursors. This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke. This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

No MeSH data available.


Related in: MedlinePlus