JAK2/STAT3 pathway is involved in the protective effects of epidermal growth factor receptor activation against cerebral ischemia/reperfusion injury in rats

Tang, Yuanyuan; Tong, Xuhui; Li, Yan; Jiang, Guojun; Yu, Man; Chen, Yinling; Dong, Shuying

doi:10.1016/j.neulet.2017.10.037

Cited by 40 publications

(28 citation statements)

References 44 publications

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“…In addition, our study showed that the phosphorylation levels of JAK2/STAT3 are downregulated after IR injury, while pretreatment with mild hypothermia and leptin can upregulate these and thus attenuate IR injury; these results confirmed that activating JAK2/-STAT3 pathway can attenuate IR injury. However, our results are in dispute with some studies, which showed that the phosphorylation levels of JAK2/STAT3 are increased after IR injury [51][52][53]. We think it has something to do with the time of the models.…”

Section: Discussioncontrasting

confidence: 99%

Mild Hypothermia Attenuates Hepatic Ischemia–Reperfusion Injury through Regulating the JAK2/STAT3-CPT1a-Dependent Fatty Acid β-Oxidation

Wang

Xia

et al. 2020

Oxidative Medicine and Cellular Longevity

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Hepatic ischemia–reperfusion (IR) injury is a clinical issue that can result in poor outcome and lacks effective therapies at present. Mild hypothermia (32–35°C) is a physiotherapy that has been reported to significantly alleviate IR injury, while its protective effects are attributed to multiple mechanisms, one of which may be the regulation of fatty acid β-oxidation (FAO). The aim of the present study was to investigate the role and underlying mechanisms of FAO in the protective effects of mild hypothermia. We used male mice to establish the experimental models as previously described. In brief, before exposure to in situ ischemia for 1 h and reperfusion for 6 h, mice received pretreatment with mild hypothermia for 2 h and etomoxir (inhibitor of FAO) or leptin (activator of FAO) for 1 h, respectively. Then, tissue and blood samples were collected to evaluate the liver injury, oxidative stress, and changes in hepatic FAO. We found that mild hypothermia significantly reduced the hepatic enzyme levels and the score of hepatic pathological injury, hepatocyte apoptosis, oxidative stress, and mitochondrial injury. In addition, the expression of the rate-limiting enzyme (CPT1a) of hepatic FAO was downregulated almost twofold by IR, while this inhibition could be significantly reversed by mild hypothermia. Experiments with leptin and etomoxir confirmed that activation of FAO could also reduce the hepatic enzyme levels and the score of hepatic pathological injury, hepatocyte apoptosis, oxidative stress, and mitochondrial injury induced by IR, which had the similar effects to mild hypothermia, while inhibition of FAO had negative effects. Furthermore, mild hypothermia and leptin could promote the phosphorylation of JAK2/STAT3 and upregulate the ratio of BCL-2/BAX to suppress hepatocyte apoptosis. Thus, we concluded that FAO played an important role in hepatic IR injury and mild hypothermia attenuated hepatic IR injury mainly via the regulation of JAK2/STAT3-CPT1a-dependent FAO.

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Section: Discussioncontrasting

confidence: 99%

Mild Hypothermia Attenuates Hepatic Ischemia–Reperfusion Injury through Regulating the JAK2/STAT3-CPT1a-Dependent Fatty Acid β-Oxidation

Wang

Xia

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Both Wnt/b-catenin and JAK1/STAT3 signaling pathways have been demonstrated to be implicated in the pathogenesis of IS [32,33]. Previous research has displayed Wnt/ b-catenin signaling pathway participates in the neuroprotective effects in PC-12 cells induced by amyloid-beta protein [34].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Lycium barbarum polysaccharide alleviates oxygen glucose deprivation-induced PC-12 cells damage by up-regulating miR-24

Song

Lin

Zhu

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Objective: This research was aimed to detect the functions of Lycium barbarum polysaccharides (LBPs) on oxygen and glucose deprivation (OGD) injury and potential mechanisms at PC-12 cells. Methods: CCK-8, flow cytometry and reactive oxygen species (ROS) assays were used to detect OGD, LBPs and miR-24 effects on cell viability, apoptosis, and oxidative stress. MiR-24 was transfected and texted by transfection and qRT-PCR. Moreover, the related-protein levels of apoptosis, autophagy and pathways were tested by Western blotting. Results: LBPs significantly enhanced cell viability , inhibited cell apoptosis, autophagy and ROS level in OGD injury. In addition, miR-24 expression was declined in OGD-treated cells, while it was elevated when added LBPs. The preventive effects of LBPs on PC-12 cell damage induced by OGD were reversed by down-regulating miR-24. Furthermore, miR-24 inhibitor declined LBPs-induced change in Wnt/b-catenin and JAK1/STAT3 pathways in OGD-injuried cells. Conclusions: LBPs exhibited preventive effects via up-regulating miR-122 and activating Wnt/b-catenin and JAK1/STAT3 pathways in OGD-induced PC-12 cells. ARTICLE HISTORY

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“…STAT3 signal transduction pathway is activated in a variety of primary tumors and tumor derived cell lines [34], which plays an important role in the regulation of tumor cell growth, proliferation and apoptosis process, this is may be related to the activation of a series of target gene followed STAT3 activation [35,36]. In the recent years, there are many researches on the relationship between STAT3 and cancers, and these research suggest that the activation of STAT3 is closely associated with colorectal cancer [37]. Thus, STAT3 as a therapeutic target for colorectal cancer may provide a new therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

The mechanism and tumor inhibitory study of Lagopsis supine ethanol extract on colorectal cancer in nude mice

Wei

Wang

Xia

et al. 2019

BMC Complement Altern Med

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Background: This study was aimed to determination the tumor inhibitory effect and explore the potential mechanisms of Lagopsis supine ethanol extract (Ls) on colorectal cancer. Methods: The cell growth inhibition experiment of Ls in colorectal cancer cell lines was determined by MTT method in the time course of 24, 48 and 72 h in four gradient drug concentrations. The protein expression levels of pSTAT3, pJAK2, STAT3, JAK2, Bcl-2 and caspase 3 were measured by Western blot method. The mRNA levels of the downstream genes of STAT3 were detected through semi-quantitative RT PCR. Sixty Balb/c-nude mice were xenograft with HCT116 colorectal cancer cells through subcutaneously. The xenografts were divided into five groups: model group, positive group (capecitabine 300 mg/kg) and three dosages of Ls treated groups (75, 150 and 300 mg/kg). Tumor size and tumor weight were calculated for evaluation the anti-tumor effects. H & E staining and immunohistochemical analysis were used to determine the histopathological changes and the levels of pSTAT3 and pJAK2 in the tumor tissues. Results: Ls exhibited a significant anti-proliferation effect in HCT116 and SW480 cells in vitro. The protein levels of pSTAT3, pJAK2 and Bcl-2, and the mRNA levels of Bcl-2 and Bak notably reduced with a dose-dependent manner. While the protein levels of caspase 3, and mRNA levels of Bax and caspase-3 remarkably increased in the gradient dosage of Ls in HCT116 cells. HCT116 in vivo xenografts experiment showed that the growth of the tumors significantly inhibited by Ls administration, which with no any significant body weight changes in each experiment group. The histopathology analysis displayed that Ls significantly reduced the inflammatory cells in tumor tissue. Furthermore, Ls also significantly down-regulate the protein levels of pSTAT3 and pJAK2 in the tumor tissues, compared with the model group. Conclusions: This work shows that Ls inhibited the cell proliferation of colorectal cancer in vitro and significantly reduced the tumor growth in HCT116 xenografts in vivo, which is probably related with the JAK/STAT signal pathway.

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JAK2/STAT3 pathway is involved in the protective effects of epidermal growth factor receptor activation against cerebral ischemia/reperfusion injury in rats

Cited by 40 publications

References 44 publications

Mild Hypothermia Attenuates Hepatic Ischemia–Reperfusion Injury through Regulating the JAK2/STAT3-CPT1a-Dependent Fatty Acid β-Oxidation

Mild Hypothermia Attenuates Hepatic Ischemia–Reperfusion Injury through Regulating the JAK2/STAT3-CPT1a-Dependent Fatty Acid β-Oxidation

RETRACTED ARTICLE: Lycium barbarum polysaccharide alleviates oxygen glucose deprivation-induced PC-12 cells damage by up-regulating miR-24

The mechanism and tumor inhibitory study of Lagopsis supine ethanol extract on colorectal cancer in nude mice

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