【摘 要】
：
P2X7 receptor (P2X7r) is important in inflammation and fibrosis.The aim of the present study was to investigate the effect of P2X7r inhibition, using a specific inhibitor (A438079) to prevent the deve
【机 构】
：
Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules,Ministry of Educatio
论文部分内容阅读
P2X7 receptor (P2X7r) is important in inflammation and fibrosis.The aim of the present study was to investigate the effect of P2X7r inhibition, using a specific inhibitor (A438079) to prevent the development of liver fibrosis on human hepatic stellate cells, LX2.The supernatant from lipopolysaccharide (LPS)stimulated RAW264.7 mouse macrophages was supplemented to LX2 cells for 24 h.LX2 cells were primed with LPS for 4 h and subsequently stimulated for 30 min with 3 mmol · L1 of adenosine 5′triphosphate (ATP).A438079 (10 μmol ·L1) was supplemented to LX2 cells 10 min prior to ATP.Directly treated with LPS on LX2 cells, mRNA expressions of IL13, IL18 and IL6 were increased, as well as P2X7r.And caspase1, ASC and NLRP3 mRNA expressions were increased with LPS stimulation.LPS stimulation also increased αSMA and collagen I mRNA expressions.Interestingly treatment of LX2 cells with mediums from LPSprimed RAW 264.7 mouse macrophages exhibited greater increase of mRNA expressions of above genes than those in LX2 directly treated with LPS.Pretreatment of directly or indirectly LPSstimulated LX2 cells with A438079 both suppressed IL1 β mRNA expression.In addition treatment of LPSprimed LX2 cells with 3 mM ATP induced the significant increase of IL1β, IL6, caspase1, pannexin1, cSMA and collagen I mRNA expression, the increasing of αSMA protein expression and cleavage of IL1β.These events were significantly suppressed by pretreatment with P2X7r antagonist A438079.P2X7r blockade also significantly reduced the protein expression of αSMA.Our results suggest that the involvement of the P2X7rNLRP3 inflammasome pathway in the secretion of IL1β from extracellular ATP/LPSstimulated human hepatic stellate cells.This study demonstrated that repression of the P2X7r represents a novel potential therapeutic approach to control liver fibrosis.
其他文献
Aim Angiotensin Ⅱ (AngⅡ) induces vascular smooth muscle cell (VSMC) migration and growth, which is responsible for vascular remodeling during some cardiovascular diseases.It has been demonstrated to a
Background and Aim Vascular smooth muscle cell (SMC) phenotype change is a hallmark of vascular remodeling, which can be regulated via MicroRNAs (miRNAs)dependent mechanism.We recently identified Asym
TP53, encoding a wellknown tumor suppressor p53, plays essential roles in tumor initiation and progression, and is frequently mutated in lung cancer.However, pharmacological stabilization and reactiva
Aim It is well known that menopause could worsen agerelated ventricular concentric remodeling and increased incidence of arrhythmias following estrogen (E2) deficiency.However, the underlying mechanis
Aim Autosomal dominant polycystic kidney disease (ADPKD) affects between 1 in 400 to 1000 individuals and is characterized by massive enlargement of fluidfilled cysts of renal tubular origin that comp
Progressive beta cell apoptosis is a major cause leading to a decline in beta cell mass in type 2 diabetes.While it has been discovered that mitochondrial protein Sirtuin 5 (SIRT5) functions as the pr
Currently, accumulating studies indicated that upregulation of glycogen synthase kinase3β (GSK3β)played an important role in depression pathogenesis.Our previous study demonstrated that ammoxetine, a
Aim Aging is the dominant risk factor for cardiovascular disease.Recently, we have shown that genomic instability, a causative mechanism of aging in general, induced by functional mutation of the ERCC
Aim DL08052 is a novel Rhokinases inhibitor which has been found to have potent cardiovascular effects.In the present research, we aimed to study the potential of DL08052 in the treatment of pulmonary
Danshen has been used in stroke treatment for thousands of years in China.However, the underlying mechanism still remains elusive.Neuron loss is the cardinal feature of stroke.Stimulating endogenous n