scholarly journals Inhibition of the SOCS1-JAK2-STAT3 Signaling Pathway Confers Neuroprotection in Rats with Ischemic Stroke

2017 ◽  
Vol 44 (1) ◽  
pp. 85-98 ◽  
Author(s):  
Xiao-Lei Wang ◽  
Chun-Mei Qiao ◽  
Jiong-Ou Liu ◽  
Chun-Yang Li
Keyword(s):  
Ischemic Stroke ◽  
Protein Expression ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Rat Model ◽  
Caspase 3 ◽  
Neuronal Cells ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Mrna And Protein Expression

Background: The present study aims to investigate the protective effects of the SOCS1-JAK2-STAT3 signaling pathway on neurons in a rat model of ischemic stroke. Methods: Our study was conducted using an ischemic stroke rat model. After the microglia were extracted, 40 neonatal Sprague-Dawley (SD) rats were assigned into the blank, AG490, model and negative control (NC) groups. The neurological function of all the rats was evaluated. Histopathological changes were observed. qRT-PCR and western blotting were applied to measure the expression of genes and proteins in the SOCS1-JAK2-STAT3 signaling pathway and related to apoptosis. The TUNEL assay was conducted to calculate the cellular morphology and apoptosis of neuronal cells. Cell viability was detected using the MTT assay. In addition, immunoassays were used to measure the content of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) as well as the levels of oxidative stress. Results: Compared with the blank group, the model and NC groups showed higher neurological function scores—the cytoplasm of the neurons were cavitated, the organelles were reduced with unclear margins, some of the neurons were necrotic, and apoptosis was increased. In addition, the NC and model groups exhibited decreased cell viability, lower mRNA and protein expression of SOCS1 SOCS3 and bcl-2 and reduced SOD and GSH levels but higher mRNA and protein expression levels of AK2, STAT3,Bax and caspase-3 as well as increased protein expression of P-JAK2, P-STAT3 and activated caspase-3 (c-caspase-3). Moreover, the MDA levels were up-regulated in the NC and model groups. In contrast, opposing trends were found in the AG490 group compared with the NC and model groups. Conclusion: These data demonstrate that inhibiting the SOCS1-JAK2-STAT3 signaling pathway can reduce the loss of nerve function and apoptosis of neuronal cells, which provides a new target for the clinical treatment of ischemic stroke.

scholarly journals MicroRNA-21 Regulates the Proliferation, Differentiation, and Apoptosis of Human Renal Cell Carcinoma Cells by the mTOR-STAT3 Signaling Pathway

2016 ◽  
Vol 24 (5) ◽  
pp. 371-380 ◽  
Author(s):  
Tao Liang ◽  
Xiao-Yong Hu ◽  
Yong-Hui Li ◽  
Bin-Qiang Tian ◽  
Zuo-Wei Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Caspase 3 ◽  
Human Renal Cell Carcinoma ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

MicroRNA-21 (miRNA-21), a kind of short, noncoding RNAs, functioned as a tumor marker and was upregulated in renal cell carcinoma (RCC). However, the underlying mechanisms of miRNA-21 in RCC were uncertain. Therefore, the effects and mechanisms of miRNA-21 on the proliferation, differentiation, and apoptosis of cultured human RCC cells were further investigated in this study. After slicing miRNA-21 in RCC cells, the viability, mRNA expression of C/EBPα and PPARγ, caspase 3 activity, and protein expression of mTOR, STAT3, and pSTAT3 were determined. It was found that knockdown of miRNA-21 downregulated the optical density (OD) value of cells, inhibited mRNA expression of PPARγ and C/EBPα, and enhanced activity of caspase 3. Furthermore, protein expression of pSTAT3 was also decreased in the absence of miRNA-21. Notably, miRNA-21-changed proliferation, differentiation, and apoptosis of human RCC cells were partially regulated following the block of the mTOR-STAT3 signaling pathway by the mTOR inhibitor (XL388). It was indicated that miRNA-21 promoted proliferation and differentiation and decreased apoptosis of human RCC cells through the activation of the mTOR-STAT3 signaling pathway.

Mir-149 Promotes Survival and Differentiation of Bone Marrow Mesenchymal Stem Cells by Regulating Interleukin-6/Signal Transducer and Activator of Transcription 3 Signaling Pathway

2019 ◽  
Vol 9 (8) ◽  
pp. 1160-1166
Author(s):  
Guozhong Qin ◽  
Shaochuan Huo ◽  
Juehui Li ◽  
Yin Lian ◽  
Xiaoli Jin
Keyword(s):  
Bone Marrow ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Alp Activity ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Marrow Mesenchymal Stem Cells ◽  
Sirna Group

Bone marrow mesenchymal stem cells (BMSCs) can self-renew with multi-directional differentiation. Mir-149 is involved in various diseases, but whether Mir-149 regulates the survival and differentiation of BMSCs and related mechanisms remains unclear. BMSCs were isolated and randomly divided into Si-NC group, Mir-149 siRNA group, and Mir-149 siRNA + STAT3 inhibitor WP1066 group followed by analysis of the expression of Mir-149, RUNX2 and OPN mRNA by real time PCR, BMSCs proliferation by MTT assay, Caspase 3 activity, ALP activity, formation of type II collagen and IL-6 level by ELISA, as well as STAT3 signaling pathway expression by Western blot. Mir-149 expression was reduced in BMSCs of Mir-149 siRNA group, with promoted survival of BMSCs, decreased Caspase 3 activity, increased expression of RUNX2 and OPN, type II collagen formation, ALP activity, IL-6 secretion, as well as elevated pSTAT3 phosphorylation. The differences were statistically significant compared to Si-NC group (P < 0.05). Mir-149 siRNA + WP1066 inhibited pSTAT3 phosphorylation, reduced BMSCs survival, increased Caspase 3 activity, decreased RUNX2 and OPN expression, type II collagen production, ALP activity, as well as reduced IL-6 secretion. Compared with Mir-149 siRNA group, there were significant differences (P < 0.05). Down-regulation of Mir-149 in BMSCs can promote BMSCs survival and osteogenic differentiation by regulating IL-6/STAT3 signaling pathway.

scholarly journals Oxyresveratrol induces apoptosis and inhibits cell viability via inhibition of the STAT3 signaling pathway in Saos‑2 cells

2020 ◽  
Vol 22 (6) ◽  
pp. 5191-5198
Author(s):  
Tao Lv ◽  
Zhen Jian ◽  
Dejian Li ◽  
Rongguang Ao ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals JAK2/STAT3 Signaling Pathway Plays a Key Role in Nicotine Mediated Neuroinflammation Suppression in an Ischemic Rat Model

2021 ◽  
Author(s):  
Qi Wang ◽  
Tingting Han ◽  
Ruihe Lai ◽  
Dalong Zhang ◽  
Yao Diao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Signaling Pathway ◽  
Rat Model ◽  
Inflammatory Factors ◽  
Spatial Learning And Memory ◽  
Sham Operation ◽  
Micropet Imaging ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Significant Difference

Abstract BackgroundTo explore the mechanism of nicotine mediated improvement of cognitive impairment in an established ischemic rat model. MethodsEndothelin-1 (ET-1) was injected into the left thalamic region in adult male Sprague-Dawley (SD) rats to establish ischemia model. 6 groups of rats (6 rats in each group) were then treated with nicotine, nicotine+DHβE, DHβE, AG490, nicotine +AG490 and saline respectively via intraperitoneal injection for 9 days. Another sham operation group was treated with saline as above. Morris Water Maze (MWM) test was performed for 6 consecutive days starting on the 4th day after operation to detect the cognitive function of rats in each group. 2-[18F]-A-85380 microPET imaging was performed on day 10 to evaluate the changes of α4β2 nAChRs in different brain regions of rats. Real-time PCR and Western blot were used to detect the amount of α4β2 nAChRs, JAK2, STAT3 and inflammatory factors in thalamus of rats in each group. ResultsThe results of MWM test showed the spatial learning and memory abilities of rats in the nicotine and sham operation groups were significantly better than the saline treating group in this ischemic rat model (p<0.05). There was no significant difference in other groups (p>0.05). MicroPET imaging showed more uptake of 2-[18F]-A-85380 in the nicotine, nicotine+AG490 and sham operation groups than in saline treating group, while there was no significant difference found in other groups (p>0.05). The expression of α4- and β2-nAChR in nicotine, nicotine+AG490 and sham operation groups was significantly higher than the saline treating group (p<0.05). In the nicotine group, the expression of p-JAK2 and p-STAT3 in left thalamus of rats was significantly higher than the saline treating group (p<0.05), and the expression of IL-1β and IL-6 protein was found to be lower than the saline treating group (p<0.05). While the expression of p-JAK2, p-STAT3 and inflammatory factors was not significantly different in all the other groups (p>0.05). ConclusionThe study suggests nicotine inhibits the expression of inflammatory factors by activating α4β2 nAChRs through the activation of JAK2-STAT3 signaling pathway to improve cognitive impairment in ischemic rats.

miR126-Mediated Signal Transducer and Activator of Transcription 3 Signaling Pathway Regulates the Malignant Biological Behavior of Pancreatic Cancer Cells

2020 ◽  
Vol 10 (8) ◽  
pp. 1199-1205
Author(s):  
Demao Kong ◽  
Xia Wang
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Plasmid Transfection ◽  
Low Expression

Background and purpose: As a type of non-coding genetic material widely existing in eukaryotes, a growing amount of research have confirmed that it have close connection with the occurrence and progression of various malignancies. MicroRNA126 is increased in non-small-cell lung cancer, liver cancer and gastric carcinoma. The up-regulation of miR126 in cervical cancer is closely associated with the clinical staging, histological grade, depth of invasion and early metastasis of the tumor, and it is also of great value in predicting the survival prognosis of the tumor. However, there is little known about the relationship between miR126 and pancreatic carcinoma. Therefore, this study explored the miR126-mediated STAT3 signaling pathway in medicating pancreatic cancer cell multiplication, migration, cell cycle and apoptosis in vitro . Methods: PANC-1 cell (human pancreatic cancer cell line) was selected for routine resuscitation and subculture. The experiment is grouped as: blank control group (NC group), empty plasmid transfection group (miR126-NC group), miR126mimic transfection group (overexpression Group) and miR126 inhibition plasmid transfection group (low expression group); cell viability of each group for 12 h, 24 h, 48 h and 72 h was detected using MTT assay. Wound healing assay was used to evaluated the ability of cell migration. Flow cytometry was performed to analyze cell cycle. The mRNA expression of Caspase-3 was determined by reverse transcription PCR (RT-PCR). STAT3 protein was evaluated by western blot. Results: miR126 overexpression significantly increased cell proliferation at 12 h, 24 h, 48 h, and 72 h, while the cell proliferation rates of the low expression group at each time point were significantly reduced in comparision with those of the NC group and the miR126-NC group (P < 0 05). miR126 overexpression significantly induced cell migration, while miR126 low-expression significantly inhibited cell migration (P < 0 05). miR126 overexpression significantly enhanced the percentage of G2/M, while the percentage of G2/M in the low-expressed group was remarkably reduced in comparision with those of the NC group and the miR126-NC group (P < 0 05). The mRNA expression of Caspase-3 was significantly inhibited in miR126 overexpression group, while the expression of Caspase-3 mRNA in the cells with miR126 low expression was remarkably increased (P < 0 05). The protein expression of STAT3 in miR126 overexpression group was notably up-regulated, while the expression level of STAT3 protein in the low expression group was prominently down-regulated (P <0 05). Conclusion: MiR126 overexpression may induces the STAT3 signaling pathway and then regulates cell proliferation, cell migration, cell cycle arrest and cell apoptosis in pancreatic carcinoma.

scholarly journals β-Elemene Triggers ROS-dependent Apoptosis in Glioblastoma Cells Through Suppressing STAT3 Signaling Pathway

2021 ◽  
Vol 27 ◽  
Author(s):  
Shi-zhong Cai ◽  
Qian-wei Xiong ◽  
Li-na Zhao ◽  
Yi-ting Ji ◽  
Zheng-xiang Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Treatment Strategies ◽  
Oxygen Species ◽  
Glioblastoma Cells ◽  
Western Blot Assay ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Apoptotic Activity ◽  
Induced Apoptosis

Glioblastoma is one of the most aggressive primary brain tumors with few treatment strategies. β-Elemene is a sesquiterpene known to have broad spectrum antitumor activity against various cancers. However, the signaling pathways involved in β-elemene induced apoptosis of glioblastoma cells remains poorly understood. In this study, we reported that β-elemene exhibited antiproliferative activity on U87 and SHG-44 cells, and induced cell death through induction of apoptosis. Incubation of these cells with β-elemene led to the activation of caspase-3 and generation of reactive oxygen species (ROS). Western blot assay showed that β-elemene suppressed phosphorylation of STAT3, and subsequently down-regulated the activation of p-JAK2 and p-Src. Moreover, pre-incubation of cells with ROS inhibitor N-acetyl-L-cysteine (NAC) significantly reversed β-elemene-mediated apoptosis effect and down-regulation of JAK2/Src-STAT3 signaling pathway. Overall, our findings implied that generation of ROS and suppression of STAT3 signaling pathway is critical for the apoptotic activity of β-elemene in glioblastoma cells.

scholarly journals Da Cheng Qi Decoction Alleviates Cerulein-Stimulated AR42J Pancreatic Acinar Cell Injury via the JAK2/STAT3 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Zehua Zhou ◽  
Ying Chen ◽  
Wenmin Dong ◽  
Rui An ◽  
Kun Liang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Acinar Cell ◽  
Biochemical Markers ◽  
Cell Injury ◽  
Pancreatic Acinar Cell ◽  
Stat3 Pathway ◽  
Jak2 Inhibitor ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Background. Acute pancreatitis (AP) is a common acute abdomen inflammation, characterized by the dysregulation of digestive enzyme production and secretion. Many studies have shown that Da Cheng Qi Decoction (DCQD) is a secure, effective prescription on AP. In this study, cerulein-stimulated AR42J cells damage model was established to further explore the feasibility and underlying mechanism of DCQD as a potential inhibitor of JAK2/STAT3 pathway for the treatment of AP. Methods. Cell viability of DCQD was measured using a cell counting Kit-8 assay. Pancreatic biochemical markers such as amylase, lipase, and C-reactive protein production were measured by assay kits, respectively. Cytokines (TNF-α, IL-6, IL-10, and IL-1β) were assayed by ELISA. Protein location and protein expression were detected by immunofluorescence staining and Western blotting, respectively. Gene expression was assessed by real-time PCR. For mechanistic analysis of the effect of DCQD on JAK2/STAT3 signaling pathway, selective JAK2 inhibitor (Fedratinib) and STAT3 inhibitor (Stattic) as well as STAT3 activator (Garcinone D) were used. Results. DCQD protected cells by regulating cerulein-induced inflammation and reducing the secretion of pancreatic biochemical markers. Moreover, DCQD could not only inhibit the nuclear translocation of p-STAT3, but also decrease the mRNA expression of JAK2 and STAT3 as well as the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in protein level. Additionally, DCQD could regulate the mRNA and protein expression of JAK2/STAT3 downstream effectors, Bax and Bcl-XL. The activated effect of cerulein on JAK2/STAT3 pathway was also reversed by JAK2 inhibitor Fedratinib or STAT3 inhibitor Stattic. And the overexpression of JAK2/STAT3 pathway, via STAT3 activator Garcinone D, did exert damage on cells, which bore a resemblance to cerulein. Conclusion. The activation of JAK2/STAT3 pathway may play a key role in the pathogenesis of cerulein-stimulated AR42J pancreatic acinar cell injury. DCQD could improve inflammatory cytokines and cell injury, which might be mediated by suppressing the activation of JAK2/STAT3 signaling pathway.

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