Gene interactions and pathways from curated databases and text-mining
Invest Ophthalmol Vis Sci 2009, PMID: 19098317

Role of PI3K/Akt and MEK/ERK in mediating hypoxia-induced expression of HIF-1alpha and VEGF in laser-induced rat choroidal neovascularization.

Yang, Xiu-Mei; Wang, Yu-Sheng; Zhang, Jian; Li, Yan; Xu, Jian-Feng; Zhu, Jie; Zhao, Wei; Chu, Da-Ke; Wiedemann, Peter

OBJECTIVE

The transcription factor hypoxia-inducible factor (HIF)-1 plays a central physiological role in oxygen and energy homeostasis and is activated during hypoxia by stabilization of the subunit HIF-1alpha. Hypoxia plays an important role in the development of choroidal neovascularization (CNV). Expression of HIF-1alpha has been demonstrated in CNV. Vascular endothelial growth factor (VEGF) is one of the most well-characterized angiogenic factors in CNV, which is under the regulation of HIF-1. The aim of the present study was to explore the upstream signaling pathways involved in regulating hypoxia-induced expression of HIF-1alpha and VEGF in laser-induced rat CNV.

METHODS

A well-established rat model of CNV and cultured human retinal pigment epithelium (hRPE) was used to investigate the role of PI3K/Akt and MEK/ERK pathways in regulating HIF-1alpha and VEGF expression in CNV in rat and hRPE under hypoxia by immunohistochemistry, Western blot analysis, real-time PCR, and ELISA.

RESULTS

pAkt, pERK, HIF-1alpha, and VEGF were upregulated in vivo and in vitro. PI3K inhibitor (Ly294002) significantly decreased pAkt activity and HIF-1alpha and VEGF expression in vivo and in vitro, whereas MEK inhibitor (PD98059) reduced ERK phosphorylation and the expression of VEGF but had no effect on HIF-1alpha. LY294002 and PD98059 severely inhibited the formation of CNV.

CONCLUSIONS

The PI3K/Akt pathway was required for hypoxia-induced expression of HIF-1alpha and VEGF, whereas the MEK/ERK pathway was required only for VEGF in laser-induced rat CNV.

Diseases/Pathways annotated by Medline MESH: Anoxia, Choroidal Neovascularization, Disease Models, Animal
Document information provided by NCBI PubMed

Text Mining Data

VEGF → MEK/ERK: " Role of PI3K/Akt and MEK/ERK in mediating hypoxia induced expression of HIF-1alpha and VEGF in laser induced rat choroidal neovascularization "

VEGF → PI3K/Akt: " Role of PI3K/Akt and MEK/ERK in mediating hypoxia induced expression of HIF-1alpha and VEGF in laser induced rat choroidal neovascularization "

VEGF → PI3K/Akt: " Role of PI3K/Akt and MEK/ERK in mediating hypoxia induced expression of HIF-1alpha and VEGF in laser induced rat choroidal neovascularization "

HIF-1alpha → MEK/ERK: " Role of PI3K/Akt and MEK/ERK in mediating hypoxia induced expression of HIF-1alpha and VEGF in laser induced rat choroidal neovascularization "

HIF-1alpha → PI3K/Akt: " Role of PI3K/Akt and MEK/ERK in mediating hypoxia induced expression of HIF-1alpha and VEGF in laser induced rat choroidal neovascularization "

HIF-1alpha → PI3K/Akt: " Role of PI3K/Akt and MEK/ERK in mediating hypoxia induced expression of HIF-1alpha and VEGF in laser induced rat choroidal neovascularization "

hypoxia-inducible factor (HIF)-1 → HIF-1alpha: " The transcription factor hypoxia-inducible factor (HIF)-1 plays a central physiological role in oxygen and energy homeostasis and is activated during hypoxia by stabilization of the subunit HIF-1alpha "

VEGF ⊣ PI3K/Akt: " A well established rat model of CNV and cultured human retinal pigment epithelium ( hRPE ) was used to investigate the role of PI3K/Akt and MEK/ERK pathways in regulating HIF-1alpha and VEGF expression in CNV in rat and hRPE under hypoxia by immunohistochemistry, Western blot analysis, real-time PCR, and ELISA "

VEGF ⊣ PI3K/Akt: " A well established rat model of CNV and cultured human retinal pigment epithelium ( hRPE ) was used to investigate the role of PI3K/Akt and MEK/ERK pathways in regulating HIF-1alpha and VEGF expression in CNV in rat and hRPE under hypoxia by immunohistochemistry, Western blot analysis, real-time PCR, and ELISA "

HIF-1alpha ⊣ PI3K/Akt: " A well established rat model of CNV and cultured human retinal pigment epithelium ( hRPE ) was used to investigate the role of PI3K/Akt and MEK/ERK pathways in regulating HIF-1alpha and VEGF expression in CNV in rat and hRPE under hypoxia by immunohistochemistry, Western blot analysis, real-time PCR, and ELISA "

HIF-1alpha ⊣ PI3K/Akt: " A well established rat model of CNV and cultured human retinal pigment epithelium ( hRPE ) was used to investigate the role of PI3K/Akt and MEK/ERK pathways in regulating HIF-1alpha and VEGF expression in CNV in rat and hRPE under hypoxia by immunohistochemistry, Western blot analysis, real-time PCR, and ELISA "

Manually curated Databases

No curated data.