Ligustrazine Suppresses Platelet-Derived Growth Factor-BB-Induced Pulmonary Artery Smooth Muscle Cell Proliferation and Inflammation by Regulating the PI3K/AKT Signaling Pathway

2021 ◽  
pp. 1-23
Author(s):  
Huiping Huang ◽  
Lingjin Kong ◽  
Shaohua Luan ◽  
Chuanzong Qi ◽  
Fanrong Wu
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Right Ventricular ◽  
Signaling Pathway ◽  
Ventricular Hypertrophy ◽  
Akt Signaling ◽  
Platelet Derived Growth Factor ◽  
Akt Signaling Pathway ◽  
Pulmonary Artery Smooth Muscle

Pulmonary arterial hypertension (PAH) is a serious pulmonary vascular disease. Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role in the course of this disease. Ligustrazine is an alkaloid monomer extracted from the rhizome of the herb Ligusticum chuanxiong. It is often used to treat cardiovascular diseases, but its effect on PAH has rarely been reported. This study aims to explore the protective effect and mechanism of ligustrazine on PAH. In the in vivo experiment, monocrotaline (MCT) was used to induce PAH in rats, and then ligustrazine (40, 80, 160 mg/kg/day) or sildenafil (25 mg/kg/day) was administered. Four weeks later, hemodynamic changes, right ventricular hypertrophy index, lung morphological characteristics, inflammatory factors, phosphoinositide 3-kinase (PI3K), and AKT expression were evaluated. In addition, primary rat PASMCs were extracted by the tissue adhesion method, a proliferation model was established with platelet-derived growth factor-BB (PDGF-BB), and the cells were treated with ligustrazine to investigate its effects on cell proliferation, inflammation, and cell cycle distribution. The results indicate that ligustrazine can markedly alleviate right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodeling, and inflammation caused by MCT, and that it decreased PI3K and AKT phosphorylation expression. Moreover, ligustrazine can inhibit the proliferation and inflammation of PASMCs and arrest the progression of G0/G1 to S phase through the PI3K/AKT signaling pathway. Therefore, we conclude that ligustrazine may inhibit the proliferation and inflammation of PASMCs by regulating the activation of the PI3K/AKT signaling pathway, thereby attenuating MCT-induced PAH in rats. Collectively, these findings suggest that ligustrazine may be a promising therapeutic for PAH.

miR-223 Promotes Smooth Muscle Cell Proliferation and Atherosclerotic Plaque Formation by Inhibiting Phosphatase and Tensin Homolog (PTEN)/ Phosphatidylinositol 3-Kinase (PI3K) and Protein Kinase B (AKT) Signaling Pathway

2020 ◽  
Vol 10 (5) ◽  
pp. 719-723
Author(s):  
Xiaofang Tao ◽  
Nianhua Fei
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Plaque Formation ◽  
Akt Signaling Pathway ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Sd Rats ◽  
Vsmcs Proliferation

Abnormal vascular smooth muscle cells (VSMCs) proliferation is the pathological basis of atherosclerosis (AS) pathogenesis. miR-223 is abnormally expressed in AS plaques and affects the proliferation of VSMCs, but the mechanism of miR-223 affecting the proliferation of VSMCs is unclear. Our study intends to investigate the mechanism of miR-223 in VSMCs proliferation and AS formation. Healthy SD rats and miR-223 knockout SD rats took high-fat diet to induce AS model. Oil red O staining was done to observe AS formation. miR-223 mimics/NC was transferred to VSMCs followed by analysis of miR-214 expression by real-time PCR, cell proliferation by CCK8 assay, phosphatase and tensin homolog gene (PTEN) level by Western blot detection. Compared with control group, after knocking out miR-223, the AS level was significantly decreased and PTEN expression was significantly elevated (P < 0 05). After transfection of miR-223 mimics into VSMCs, PTEN expression protein was significantly decreased and the number of cells was increased (P < 0 05). In addition, the luciferase signal of miR-223 mimics and pmirGLO-PTEN-3 UTR-wt co-transfection group was significantly reduced (P < 0 05). miR-223 promotes VSMCs proliferation and AS plaque formation by targeting PTEN/PI3K/Akt signaling pathway.

scholarly journals MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

2018 ◽  
Vol 50 (6) ◽  
pp. 2365-2389 ◽  
Author(s):  
Ying  Liu ◽  
Yi Miao ◽  
Xin Gao ◽  
Yuan-Yuan Wang ◽  
Huan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Bioinformatics Analysis ◽  
Airway Remodeling ◽  
Akt Signaling ◽  
Airway Smooth Muscle Cells ◽  
Akt Signaling Pathway ◽  
Tgf Β1

Background/Aims: The etiology of asthma, which is a complicated disorder with various symptoms, including wheezing, coughing, and airflow obstruction, remains poorly understood. In addition, the effects of microRNAs (miRs) have not been explored. This study explored the effect of microRNA-200a (miR-200a) on airway smooth muscle cells (ASMCs) and airway remodeling in asthmatic mice. Furthermore, we speculated that miR-200a achieves its effect by targeting FOXC1 via the PI3K/AKT signaling pathway based on differentially expressed gene screening, target miR predictions and a bioinformatics analysis. Methods: Eighty mice were assigned to a saline group or an ovalbumin (OVA) group, and the OVA group was transfected with a series of inhibitors, activators, and siRNAs to test the established mouse model. Airway reactivity and the ratio of eosinophils (EOSs) to leukocytes were detected. An ELISA was adopted to measure the levels of interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor (TNF)-α, and immunoglobulin E (IgE). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1, TGF-β1 and p-AKT in ASMCs. Finally, CCK-8 assays were performed to detect cell proliferation and flow cytometry to detect apoptosis and cell cycle entry. Results: The bioinformatics analysis indicated that miR-200a mediated the PI3K/AKT signaling pathway by targeting FOXC1. In addition, mouse models of asthma were established. An elevated expression of miR-200a, a decreased mRNA and protein expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1 and TGF-β1, a decreased expression of p-AKT, suppressed cell proliferation, accelerated apoptosis, and an increased number of cells at the G0/G1 phase were observed following the upregulation of miR-200a and downregulation of FOXC1. Conclusion: The overexpression of miR-200a may downregulate FOXC1, thereby inhibiting the activation of the PI3K/AKT signaling pathway and ultimately suppressing ASMC proliferation and airway remodeling in asthmatic mice. This evidence supports the potential that miR-200a represents a new approach to treating asthma.

scholarly journals Sphingosine-1-phosphate induces the migration and angiogenesis of EPCs through the Akt signaling pathway via sphingosine-1-phosphate receptor 3/platelet-derived growth factor receptor-β

2015 ◽  
Vol 20 (4) ◽  
Author(s):  
Hang Wang ◽  
Ke-Yin Cai ◽  
Wei Li ◽  
Hao Huang
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Akt Signaling ◽  
Platelet Derived Growth Factor ◽  
Akt Signaling Pathway ◽  
Akt Inhibitor ◽  
Sphingosine 1 Phosphate

AbstractEndothelial progenitor cells (EPCs) play a fundamental role in neoangiogenesis and tumor angiogenesis. Through the sphingosine-1-phosphate receptor 3 (S1PR3), sphingosine-1-phosphate (S1P) can stimulate the functional capacity of EPCs. Platelet-derived growth factor receptor-beta (PDGFR-β) contributes to the migration and angiogenesis of EPCs. This study aimed to investigate whether S1P induces the migration and angiogenesis of EPCs through the S1PR3/PDGFR-β/Akt signaling pathway. We used the Transwell system and the Chemicon In Vitro Angiogenesis Assay Kit with CAY10444 (an S1PR3 antagonist), AG1295 (a PDGFR kinase inhibitor) and sc-221226 (an Akt inhibitor) to examine the role of the S1PR3/PDGFR-β/Akt pathway in the S1Pinduced migration and angiogenesis of EPCs.

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