Akt regulates β-catenin in a rat model of focal cerebral ischemia-reperfusion injury

Abstract

Abstract. The present study aimed to investigate the effects of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway on the Wnt/β-catenin signaling pathway in rats with focal cerebral ischemia-reperfusion injury. A total of 96 rat focal cerebral ischemia-reperfusion models, established according to a modified version of Longa's method, were randomly divided into four groups: Sham-operated (S), cerebral ischemia-reperfusion injury (I), cerebral ischemia-reperfusion + basic fibroblast growth factor (bFGF) post-processing and, finally, cerebral ischemia-reperfusion + bFGF post-processing + PI3K inhibitor LY294002 (LY). Each group consisted of 24 rats and each group was divided into four subgroups according to the indicated reperfusion times of 12, 24, 48 and 72 h. The morphological changes of the cortical tissue and the cellular apoptosis were determined using hematoxylin and eosin staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling method, respectively. The expression levels of phosphorylated (p-)Akt, glycogen synthase kinase-3β (GSK-3β) mRNA and β-catenin in the cortical tissue were detected at different time-points. The number of apoptotic cells and the expression levels of p-Akt, GSK-3β mRNA and β-catenin in the I and LY groups were significantly higher compared with those in the S group (P<0.05). In the bFGF group, the number of apoptotic cells and the mRNA expression levels of GSK-3β were significantly decreased, whereas the expression levels of p-Akt and β-catenin were significantly increased compared with those in the I and LY groups (P<0.05). In cerebral ischemia-reperfusion injury, the PI3K/Akt signaling pathway regulated β-catenin, the main member of the Wnt signaling pathway, via GSK-3β, providing information to assist in further investigation of the mechanism of β-catenin in ischemia-reperfusion injury.

Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes

“…FGF2 and downstream PI3K/AKT signals provide the neuroprotective effect against cerebral ischemia (Xing et al, 2015 ). Our western blot results showed the distinct lower level of FGF2 in the periinfarct cortex of model rats compared with the sham group ( p < 0.05).…”

“…By contrast, A2 astrocytes possess the anti-inflammatory property and initiate endogenous neurorestorative processes including angiogenesis and neurogenesis (Liu and Chopp, 2016 ; Liddelow and Barres, 2017 ; Michinaga and Koyama, 2019 ). Studies have also documented that fibroblast growth factor 2 (FGF2) derived from A2 astrocytes plays a key role in stimulating cell proliferation and differentiation via the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathway (Xing et al, 2015 ; Zhao et al, 2019 ). Hence, inducing the transformation of astrocytes into the anti-inflammatory A2 subtype, possessing an excellent role in NVU preservation and neurovascular remodeling after ischemic stroke.…”

Sirt3 inhibits cerebral ischemia-reperfusion injury through normalizing Wnt/β-catenin pathway and blocking mitochondrial fission

“…In contrast, inhibiting the Wnt pathway represses angiogenesis and proliferation in brain microvascular endothelial cells via blocking the VEGF/CREB/ Egr-3/VCAM1 signaling pathways (Kang et al 2014). In addition, Wnt signaling has been found to be a downstream effector of the PI3K/Akt pathway, a classical antiapoptotic signaling pathway in cerebral IRI (Xing et al 2015). These data identify that the Wnt/β-catenin signaling pathway may be required for neuroprotection in cerebral IRI.…”

LncRNA CEBPA‐AS1 alleviates cerebral ischemia‐reperfusion injury by sponging miR‐340‐5p regulating APPL1/LKB1/AMPK pathway

“…miR‐340‐5p is known to regulate the expressions of ABCB5, β‐catenin, and BMP4. Coincidentally, Xing et al suggest that the AKT signaling pathway can regulate the expression of β‐catenin and further affect the progress of focal CIRI injury 24 . Furthermore, miR‐340‐5p may play a role in the regulation of BMP4 expression by negatively regulating the differentiation of rat NSCs into neurons 25 .…”

“…Coincidentally, Xing et al suggest that the AKT signaling pathway can regulate the expression of βcatenin and further affect the progress of focal CIRI injury. 24 Furthermore, miR-340-5p may play a role in the regulation of BMP4 expression by negatively regulating the differentiation of rat NSCs into neurons. 25 Commonly, the proliferating endogenous neural stem cells of the central nervous system lack self-repairing ability after brain ischemia.…”