scholarly journals YQWY Decoction Improves Myocardial Remodeling via Activating the IL-10/Stat3 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
He Li ◽  
Zhi-Jun Gong ◽  
Yun He ◽  
Jing-Jing Huang ◽  
Yu-Ning Jiang ◽  
...  
Keyword(s):  
Left Ventricular Function ◽  
Ventricular Function ◽  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Caspase 3 ◽  
Left Ventricular ◽  
Collagen I ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α

Heart failure (HF) has been known as a global health problem, and cardiac remodeling plays an essential role in the development of HF. We hypothesized that YQWY decoction might exert a cardioprotective effect against myocardium inflammation, fibrosis, and apoptosis via activating the interleukin-10 (IL-10)/Stat3 signaling pathway. To test this hypothesis, the HF model in rats was established by pressure overload through the minimally invasive transverse aortic constriction (MTAC). Echocardiography was performed to assess the left ventricular function of rats. Myocardial fibrosis in rats was observed by Masson and Picrosirius red staining, and the degree of myocardial apoptosis was detected via TUNEL staining. In addition, expression levels of IL-10, tumor necrosis factor-α (TNF-α), Stat3 (P-Stat3), P65 (P-P65), CD68, collagen I, TGF-β, CTGF, Bax, Bcl-2, cleaved caspase-3, and PARP in rat serum and myocardium samples were examined by ELISA, western blot, and immunohistochemistry, respectively. YQWY decoction treatment significantly improved left ventricular function in HF rats, especially in those of the high-dose group (LVEF%: 51.29 ± 5.876 vs. 66.02 ± 1.264, P < 0.01 ;, LVFS%: 27.75 ± 3.757 vs. 37.76 ± 1.137, P < 0.01 ). Furthermore, YQWY decoction markedly inhibited MTAC-induced myocardial fibrosis as evidenced by downregulated collagen I, TGF-β, and CTGF in myocardium and alleviated apoptosis (downregulated caspase-3 and PARP and increased Bcl-2/Bax ratio in cardiomyocytes). In addition, YQWY decoction decreased the level of the proinflammatory cytokine TNF-α in both circulating blood and myocardium and attenuated infiltration of inflammatory cells in heart tissue from HF rats. Most importantly, YQWY decoction suppressed MTAC-induced NF-κB activation and phosphorylated Stat3 by upregulating IL-10 in rat heart tissues. Our study showed that YQWY decoction could attenuate MTAC-induced myocardial inflammation, fibrosis, apoptosis, and reverse the impairment of cardiac function in rats by activating the IL-10/Stat3 signaling pathway and improving myocardium remodeling. Our findings suggested a therapeutic potential of YQWY decoction in HF.

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.

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.

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.

Myocardial T2* is not affected by ageing, myocardial fibrosis, or impaired left ventricular function

2010 ◽  
Vol 32 (5) ◽  
pp. 1095-1098 ◽  
Author(s):  
Paul Kirk ◽  
Gillian C. Smith ◽  
Michael Roughton ◽  
T. He ◽  
Dudley J. Pennell
Keyword(s):  
Left Ventricular Function ◽  
Ventricular Function ◽  
Myocardial Fibrosis ◽  
Left Ventricular ◽  
Impaired Left Ventricular Function
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