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

Therapy with miR-107 Improves Angiogenesis after pMCAO.(A) TTC staining. (B) Quantitative analysis showed that agomir-107 treatment significantly reduced the infarct volume as compared to the agomir negative control group (agomir-ctl). (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. *P < 0.05, vs. agomir-ctl group. (E) Scheme of miR-107-regulated target and down-stream signaling cascades.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Therapy with miR-107 Improves Angiogenesis after pMCAO.(A) TTC staining. (B) Quantitative analysis showed that agomir-107 treatment significantly reduced the infarct volume as compared to the agomir negative control group (agomir-ctl). (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. *P < 0.05, vs. agomir-ctl group. (E) Scheme of miR-107-regulated target and down-stream signaling cascades.

Mentions: Upregulation of miR-107 by injecting agomir-107 into lateral ventricles resulted in increased number of capillaries in IBZ as compared with agomir control group (Fig. 6A,B, P < 0.05). Further detection showed that overall infarct volume in miR-107 treatment group was significantly reduced compared to agomir control group. (Fig. 6C,D, P < 0.05). A schematic summary of our findings is presented as Fig. 6E.


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)

Therapy with miR-107 Improves Angiogenesis after pMCAO.(A) TTC staining. (B) Quantitative analysis showed that agomir-107 treatment significantly reduced the infarct volume as compared to the agomir negative control group (agomir-ctl). (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. *P < 0.05, vs. agomir-ctl group. (E) Scheme of miR-107-regulated target and down-stream signaling cascades.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Therapy with miR-107 Improves Angiogenesis after pMCAO.(A) TTC staining. (B) Quantitative analysis showed that agomir-107 treatment significantly reduced the infarct volume as compared to the agomir negative control group (agomir-ctl). (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. *P < 0.05, vs. agomir-ctl group. (E) Scheme of miR-107-regulated target and down-stream signaling cascades.
Mentions: Upregulation of miR-107 by injecting agomir-107 into lateral ventricles resulted in increased number of capillaries in IBZ as compared with agomir control group (Fig. 6A,B, P < 0.05). Further detection showed that overall infarct volume in miR-107 treatment group was significantly reduced compared to agomir control group. (Fig. 6C,D, P < 0.05). A schematic summary of our findings is presented as Fig. 6E.

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