Effects of miR-153 on angiogenesis in MCAO rats through Shh signaling pathway

B.-X. Wang, J.-J. Xu, J. Hu, M.-L. Hu, J.-M. Huang, X.-D. Zhu

Department of Neurology, The First Hospital of Jiaxing, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China. cjmcofnggpmraa@sina.com

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• Neurology

OBJECTIVE: Cerebrovascular disease is a disease which has the highest mortality in China. Angiogenesis in the ischemic region after cerebral infarction is closely related to its prognosis. Recent studies found that microRNAs (miRNAs) are involved in the regulation of neovascularization. MicroRNA-153 (MiR-153) has protective effects on the ischemic injury, but its relationship with the Sonic Hedgehog (Shh) signaling pathway is still unclear. This work aimed to investigate the role of miR-153 in angiogenesis of middle cerebral artery occlusion (MCAO) rats through the Shh signaling pathway.

MATERIALS AND METHODS: The rat cerebral ischemic injury (MCAO) model was established by thread embolism and treated by Agomir-153 and 5-EI. MiR-153 expression was detected using Real Time-Polymerase Chain Reaction (RT-PCR). The neurological function was assessed. The infarct area of the brain and the capillary density were determined using 2,3,5-triphenyl tetrazolium chloride (TTC) method. The Shh signaling pathway and angiogenesis-related factors were tested by Western blot assay.

RESULTS: Agomir-153 or Agomir-153 combined with 5-EI significantly increased miR-153 expression, reduced the infarct area, and promoted the generation of cerebral capillaries in the MCAO model. 5-EI partially blocked the protective effects of Agomir-153 and angiogenesis. The up-regulation of miR-153 markedly inhibited patched (PTC) expression and activated the Shh signaling pathway.

CONCLUSIONS: The up-regulation of miR-153 rats activated the Shh signaling pathway to promote angiogenesis and improve prognosis through lipid-coated Patch (PTC) in MCAO. MiR-153 was considered to be a new therapeutic target for promoting angiogenesis after MCAO.

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