Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson’s disease by inhibiting SP1

Abstract

Background: This study is conducted to investigate the protective role of elevated microRNA-375 (miR-375) in dopaminergic neurons in Parkinson's disease through down-regulating transcription factor specificity protein 1 (SP1). Results: The successfully modeled rats with Parkinson's disease showed aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress, and lowered dopamine content. Parkinson's disease rats treated with overexpressed miR-375 displayed improved neurobehavioral change, ameliorated neuroinflammatory response and oxidative stress, heightened dopamine content and abated neuronal apoptosis by down-regulating SP1. Up-regulation of SP1 reversed the protective effect of upregulated miR-375 on Parkinson's disease. Conclusion: Up-regulation of miR-375 ameliorated the damage of dopaminergic neurons, reduced oxidative stress and inflammation in Parkinson's disease by inhibiting SP1. Methods: Parkinson's disease rat model was established by targeted injection of 6-hydroxydopamine to damage the substantia nigra striatum. The successfully modeled Parkinson's disease rats were intracerebroventricularly injected with miR-375 mimics or pcDNA3.1-SP1. The functions of miR-375 and SP1 in neurobehavioral change, neuroinflammatory response, oxidative stress, dopamine content and expression of apoptosis-related proteins in the substantia nigra of Parkinson's disease rats were evaluated. The target relation of miR-375 and SP1 was confirmed by bioinformatics analysis and dual luciferase reporter gene assay.

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

“…Based on previous literature, SP1 overexpression promotes apoptosis by itself, and malignant cells with SP1 overexpression can avoid SP1-associated apoptosis ( Deniaud et al, 2006 ). In addition, some reports have found that SP1 was upregulated, and SP1 suppression exerted neuroprotection in experimental PD ( Yao et al, 2018 ; Cai et al, 2020 ). SP1 also favors inflammation in many pathologies ( Shin et al, 2015 ; Yang et al, 2018 ), and its absence reduces TNF-α, IL-1β, and IL-6 amounts in hypoxia-induced human umbilical vein endothelial cells (HUVECs) ( Yang et al, 2018 ).…”

“…Citron et al suggested that SP1 was expressed in cerebral tissues, with elevated amounts decreasing neuronal survival ( Citron et al, 2008 ). In addition, SP1 was shown to be upregulated in the development of neurological pathologies, including PD ( Cai et al, 2020 ; Wang et al, 2020 ) and Alzheimer’s diseases ( Ramanan and Saykin, 2013 ). Furthermore, Qin et al (2018) suggested that suppressing SP1 activation effectively inhibited OGD/R-induced inflammatory activation in microglia.…”

Silencing long noncoding RNA LINC01138 inhibits aerobic glycolysis to reduce glioma cell proliferation by regulating the microRNA‑375/SP1 axis

“…The relationship between miR-375 and SP1 has been detailed in numerous studies. miR-375 targeted SP1 to attenuate inflammatory reactions and oxidative stress, relieving the neuronal injury caused by Parkinson's disease (64). In addition, SP1 depletion was shown to decrease glucose uptake, and inhibit cell proliferation and invasion of U251MG cells by downregulating GLUT3 expression (65).…”

Specificity Protein 1: A Protein With a Two-Sided Role in Ischemic Stroke

“…SP1, a proinflammatory factor, is significantly elevated in the brain in patients with Alzheimer's disease or Parkinson's disease. It has been found that upregulation of miR-375 attenuates dopaminergic neuronal damage in Parkinson's disease by inhibiting SP1 and attenuating oxidative stress and inflammatory responses (Cai et al, 2020 ). Moreover, during spinal cord I/R injury, miRNA-128-3p exerted a neuroprotective and inflammation-reducing effect by inhibiting SP1 and reducing the proinflammatory factors IL-6, TNF-α, and IL-1β (Wang et al, 2020 ).…”