Table 2.
Roles and significance of SP1 in ischemic stroke.
| Function | Cell type | Physiological significance | Reference | |
|---|---|---|---|---|
| Protective effects | Antioxidant | Neuron and astrocyte | SP1 binds to the promoters of Znf179, GPX4, Prdx6, and TIGAR genes to increase the expression of the corresponding genes, ultimately protecting neurons through antioxidant effects. | Zou et al., 2012; Su et al., 2016; Zhou et al., 2016; Chuang et al., 2017; Jia et al., 2017; Chen et al., 2018; Wu et al., 2018 |
| Anti-apoptosis | Cerebrovascular endothelial cell | SP1 activates survivin transcription and exerts neuroprotective effects through the SP1/survivin pathway. | Mallolas et al., 2014 | |
| Preventing DNA damage | Neuron | SP1 binds to the promoter of Cox-2 and promotes Cox-2 expression, preventing DNA damage. | Lee et al., 2006 | |
| Promoting Na+/Ca2+ transporter 1 expression | Neuron | SP1 and HIF-1 together with histone acetyltransferase p300 are localized to NCX1 promoter, and NCX1 overexpression counteracts p300 inhibition-induced neural death. | Formisano et al., 2015; Shenoda, 2015 | |
| Damaging effects | Inducing BBB catabolism and inflammatory response | Astrocyte (for BBB catabolism) and neuron and microglia (for inflammatory response) | SP1 induces HIF-1 gene transcription under hypoxia. MMP-2 activated by HIF-1α-dependent mechanism can induce BBB catabolism, while HIF-1α regulates the inflammatory response through the NLRP3 inflammasome complex. | Abdullahi et al., 2018; Jiang et al., 2020 |
| Leading to cerebral edema | Astrocyte | SP1 promotes the formation of SUR1-TRPM4-AQP4 complex that increases permeability to water and ions, leading to cellular edema. | Simard et al., 2012; Woo et al., 2012; Stokum et al., 2018 | |
| Exacerbating glutamate excitotoxicity | Neuron and astrocyte | SP1 binds to the enhancer of t-PA, promoting the release of t-PA which activates NMDA receptors and exacerbating glutamate excitotoxicity. | Lopez-Atalaya et al., 2008 | |
| Constricting cerebral vessels | Cerebral artery smooth muscle | SP1 upregulates ETBR expression, which enables ET-1 to exert a vasoconstrictive effect. | Grell et al., 2014 | |