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Year : 2012  |  Volume : 60  |  Issue : 6  |  Page : 589--596

Aberrant activation of Hedgehog/Gli1 pathway on angiogenesis in gliomas

Daming Cui1, Xianzhen Chen1, Jia Yin1, Wenhua Wang1, Meiqing Lou1, Shixin Gu2 
1 Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
2 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

Correspondence Address:
Meiqing Lou
Department of Neurosurgery, Shanghai Tenth People«SQ»s Hospital, Tongji University School of Medicine, Shanghai 200072

Background: Hedgehog/Gli1 (HH/Gli1) pathway plays an important role in the patterning and development of the central nervous system during embryogenesis. Recent data have shown its potential involvement in a subset of human gliomas and inhibition of the pathway resulted in tumor suppression in both in vitro and in vivo studies. The underlying mechanisms of tumor suppression, however, remain to be fully elucidated. Materials and Methods: Gli1 expression was investigated in 60 surgically resected glioma tissues (World Health Organization (WHO) III-IV). Results: Gli1 was expressed in 43 gliomas with high Gli1 expression in nine cases, moderate expression in 21 cases, and low expression in 13 cases. Additionally, microvessel counts were higher in Gli1 positive gliomas than those in Gli1 negative gliomas. Gli1 expression in gliomas was positively correlated with microvessel density (MVD). To explore the molecular mechanisms of the phenotypic changes, we performed quantitative real-time polymerase chain reaction (PCR) and Western blot analysis to monitor the changes of a series of genes, which play critical roles in the regulation of glioma angiogenesis. In conclusion, HH/Gli1 pathway inhibition resulted in down-regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) expressions, whereas this pathway activation led to up-regulation of VEGF, MMP2, and MMP9 expressions. These molecular changes of the HH/Gli1 pathway inhibited by indirect drug approach were consistent with Gli1 RNA-interference (RNAi) in glioma cell lines. Conclusion: Our findings demonstrated that the aberrantly active HH/Gli1 pathway contributed to angiogenesis in part through induction of VEGF, MMP2, and MMP9.

How to cite this article:
Cui D, Chen X, Yin J, Wang W, Lou M, Gu S. Aberrant activation of Hedgehog/Gli1 pathway on angiogenesis in gliomas.Neurol India 2012;60:589-596

How to cite this URL:
Cui D, Chen X, Yin J, Wang W, Lou M, Gu S. Aberrant activation of Hedgehog/Gli1 pathway on angiogenesis in gliomas. Neurol India [serial online] 2012 [cited 2021 Jan 27 ];60:589-596
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