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Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury.

Ran QS, Yu YH, Fu XH, Wen YC - Neural Regen Res (2015)

Bottom Line: Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs.Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells.Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, the First People's Hospital of ZunYi/the Third Affiliated Hospital of ZunYi Medical College, Zunyi, Guizhou Province, China.

ABSTRACT
The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

No MeSH data available.


Related in: MedlinePlus

In vivo activation of the Notch signaling pathway promoted neurovascular repair in the brain after traumatic brain injury.(A) Western blot assay showing the effects of overexpression of Notch1 and Jagged1 in vivo. (B) Western blot assay showing the effects of knockdown of Notch1 and Jagged1 expression in vivo. (C) Immunofluorescence assay showing the fluorescence intensity of CD31 labeling in the Notch signaling pathway activation and inhibition groups. The fluorescence intensity of CD31 is presented as a ratio to the control group. Data are expressed as the mean ± SD (n = 5 in each group). Differences between groups were compared using one-way analysis of variance and nonparametric Mann-Whitney U test. †P < 0.05, vs. vector group. (D) Effects of Notch signaling pathway activation and inhibition in rats with traumatic brain injury (D1–D5, × 40; D6–D10, × 100). D1–D5: Arrows indicate CD31 expression. Notch1 OE: Notch1 overexpression group; Jagged1 OE: Jagged1 overexpression group; JAG1: Ligand for multipe Notch receptors and involved in the mediation of Notch signaling; siNotch1: Notch1 knockdown group; siJagged1: Jagged1 knockdown group; DAPT: γ-secretase inhibitor IX.
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Figure 5: In vivo activation of the Notch signaling pathway promoted neurovascular repair in the brain after traumatic brain injury.(A) Western blot assay showing the effects of overexpression of Notch1 and Jagged1 in vivo. (B) Western blot assay showing the effects of knockdown of Notch1 and Jagged1 expression in vivo. (C) Immunofluorescence assay showing the fluorescence intensity of CD31 labeling in the Notch signaling pathway activation and inhibition groups. The fluorescence intensity of CD31 is presented as a ratio to the control group. Data are expressed as the mean ± SD (n = 5 in each group). Differences between groups were compared using one-way analysis of variance and nonparametric Mann-Whitney U test. †P < 0.05, vs. vector group. (D) Effects of Notch signaling pathway activation and inhibition in rats with traumatic brain injury (D1–D5, × 40; D6–D10, × 100). D1–D5: Arrows indicate CD31 expression. Notch1 OE: Notch1 overexpression group; Jagged1 OE: Jagged1 overexpression group; JAG1: Ligand for multipe Notch receptors and involved in the mediation of Notch signaling; siNotch1: Notch1 knockdown group; siJagged1: Jagged1 knockdown group; DAPT: γ-secretase inhibitor IX.

Mentions: Western blot assay revealed that when Notch1 or Jagged1 overexpression constructs were injected into the brain, the corresponding protein levels were noticeably increased in brain tissue (Figure 5A). If siRNA for Notch1 or Jagged1 was injected into the brain, expression of the respective protein was knocked down (Figure 5B). Immunofluorescence staining revealed that when the Notch signaling pathway was activated in rats with mild TBI, CD31 labeling was robust compared with the control group. Conversely, when the Notch signaling pathway was suppressed, CD31 immunofluorescence was reduced (P < 0.05; Figure 5C, D).


Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury.

Ran QS, Yu YH, Fu XH, Wen YC - Neural Regen Res (2015)

In vivo activation of the Notch signaling pathway promoted neurovascular repair in the brain after traumatic brain injury.(A) Western blot assay showing the effects of overexpression of Notch1 and Jagged1 in vivo. (B) Western blot assay showing the effects of knockdown of Notch1 and Jagged1 expression in vivo. (C) Immunofluorescence assay showing the fluorescence intensity of CD31 labeling in the Notch signaling pathway activation and inhibition groups. The fluorescence intensity of CD31 is presented as a ratio to the control group. Data are expressed as the mean ± SD (n = 5 in each group). Differences between groups were compared using one-way analysis of variance and nonparametric Mann-Whitney U test. †P < 0.05, vs. vector group. (D) Effects of Notch signaling pathway activation and inhibition in rats with traumatic brain injury (D1–D5, × 40; D6–D10, × 100). D1–D5: Arrows indicate CD31 expression. Notch1 OE: Notch1 overexpression group; Jagged1 OE: Jagged1 overexpression group; JAG1: Ligand for multipe Notch receptors and involved in the mediation of Notch signaling; siNotch1: Notch1 knockdown group; siJagged1: Jagged1 knockdown group; DAPT: γ-secretase inhibitor IX.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590238&req=5

Figure 5: In vivo activation of the Notch signaling pathway promoted neurovascular repair in the brain after traumatic brain injury.(A) Western blot assay showing the effects of overexpression of Notch1 and Jagged1 in vivo. (B) Western blot assay showing the effects of knockdown of Notch1 and Jagged1 expression in vivo. (C) Immunofluorescence assay showing the fluorescence intensity of CD31 labeling in the Notch signaling pathway activation and inhibition groups. The fluorescence intensity of CD31 is presented as a ratio to the control group. Data are expressed as the mean ± SD (n = 5 in each group). Differences between groups were compared using one-way analysis of variance and nonparametric Mann-Whitney U test. †P < 0.05, vs. vector group. (D) Effects of Notch signaling pathway activation and inhibition in rats with traumatic brain injury (D1–D5, × 40; D6–D10, × 100). D1–D5: Arrows indicate CD31 expression. Notch1 OE: Notch1 overexpression group; Jagged1 OE: Jagged1 overexpression group; JAG1: Ligand for multipe Notch receptors and involved in the mediation of Notch signaling; siNotch1: Notch1 knockdown group; siJagged1: Jagged1 knockdown group; DAPT: γ-secretase inhibitor IX.
Mentions: Western blot assay revealed that when Notch1 or Jagged1 overexpression constructs were injected into the brain, the corresponding protein levels were noticeably increased in brain tissue (Figure 5A). If siRNA for Notch1 or Jagged1 was injected into the brain, expression of the respective protein was knocked down (Figure 5B). Immunofluorescence staining revealed that when the Notch signaling pathway was activated in rats with mild TBI, CD31 labeling was robust compared with the control group. Conversely, when the Notch signaling pathway was suppressed, CD31 immunofluorescence was reduced (P < 0.05; Figure 5C, D).

Bottom Line: Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs.Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells.Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, the First People's Hospital of ZunYi/the Third Affiliated Hospital of ZunYi Medical College, Zunyi, Guizhou Province, China.

ABSTRACT
The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

No MeSH data available.


Related in: MedlinePlus