HIF-1α induced by hypoxia or apoplexy inside the adenoma might be the initiating factor of invasive transformation, followed with angiogenesis for overexpressed VEGF, EMT for overexpressed PTTG, degradation of ECM for overexpressed MMPs, creating a suitable microenvironment within the tumor.
Hypoxic preconditioned (HP) BMSCs (HP-BMSCs) with increased expression of surviving factors HIF-1α and Bcl-xl (1 × 10<sup>6</sup> cells/100 μl per mouse) or cell media were administered intranasally at 3, 4, 5, and 6 days after stroke.
Our results demonstrate that GK promotes angiogenesis after ischemia stroke through increasing the expression of HIF-1α/VEGF via JAK2/STAT3 pathway, which provide an insight into the novel clinical application of GK and its analogs in ischemic stroke therapy in future.
As hypoxia inducible factor 1α (HIF-1α) is neuroprotective in stroke and mediates neuroinflammation, we tested the hypothesis that HIF-1α is a key factor of RIPC against stroke by mediating inflammation.
Integrating the compound-target network and stroke-related PPI network, we found that Akt1, HIF-1α and ITGB2 may play key roles in the treatment of stroke.
In this study, we sought to investigate the interaction of HIF-1α with MMP-2 and vascular endothelial growth factor (VEGF) in BBB injury after acute ischemia stroke.
Although the critical role of hypoxia inducible factor-1α (HIF-1α) in cerebral neovascularization after stroke has been well characterized, the details regarding the regulation of endothelial progenitor cell (EPC)-dependent neovascularization by HIF-1α are not completely understood.
Taken together, these findings reveal that HIF-1α plays a role in CIR-induced glutamate excitotoxicity via the long-lasting activation of system x<sub>c</sub><sup>-</sup> -dependent glutamate outflow and suggest that system x<sub>c</sub><sup>-</sup> is a promising therapeutic target with an extended therapeutic window in stroke.
Collectively, these results demonstrate that NCX1 expression is regulated by the Sp3/REST/HDAC1/HDAC2 complex in tMCAO and by the Sp1/HIF-1/p300 complex in PC+tMCAO and that epigenetic intervention, by modulating the acetylation of ncx1-Br, may be a strategy for the development of innovative therapeutic intervention in stroke.
Thus far, however, there is evidence that hypoxia-inducible factor-1 (HIF-1) is a nuclear factor required for transcriptional activation of several genes implicated in stroke.
Potent natural product-derived HIF-1 activators that exhibit a low level of toxicity and side effects hold promise as new treatment options for diseases such as myocardial and peripheral ischemia, and as chemopreventative agents that could be used to reduce the level of ischemia/reperfusion injury following heart attack and stroke.
HIF-1 is an essential component in changing the transcriptional repertoire of tissues as oxygen levels drop, and could prove to be a very important target for drug development, as treatments evolve for diseases, such as cancer, heart disease and stroke, in which hypoxia is a central aspect.