Study On The Role Of Growth Differentiation Factor 11 In The Pathogenesis Of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease(COPD)was a chronic inflammatory lung disease.It was reported that more than 3 million people worldwide died of chronic obstructive pulmonary disease or related diseases in 2017,which posed a huge threat and challenge to human health and family economy.The pathogenesis of COPD included:Infiltration of various inflammatory cells mainly composed of neutrophils and macrophages in the airway;various major cytokines(TNF-α,IL-6,IL-13)and inflammatory mediators significantly elevated;protease and anti-protease imbalance;oxidative damage and anti-oxidative damage imbalance,autoimmunity,apoptosis.This airway chronic inflammation destruction and tissue hyperplasia repair process ultimately led to airway remodeling and induced airflow limitation.At the same time,COPD could also be induced by a variety of external factors and body hereditary factors,but the nicotine and fine particles brought by smoking were one of the most dangerous factors.Tobacco smoke and cigarette smoke extract(CSE)had discovered more than 7,000 chemical components,including a large number of free radicals.When inhaling tobacco smoke,a large number of free radicals could cause imbalance of oxidants and antioxidants in the body.When inhaling tobacco smoke,a large amount of free radicals cause imbalance of oxidants and antioxidants in the body,and oxidative stress directly damages respiratory tract and alveolar epithelial cells.Tobacco smoke played a central role in lung injury diseases such as chronic obstructive pulmonary disease,chronic bronchitis and emphysema.In addition,Growth Differentiation Factor 11(GDF11)had been found to significantly reduce the level of expression of COPD-related genes,thereby enabling the induction of the development of COPD disease,which was involved in the development of the disease as an important gene regulatory factor.However,the molecular mechanism of the related regulatory feedback between tobacco extract and GDF11 in the development and progression of chronic obstructive pulmonary disease remained unclear,and the further research was needed.Research purposesThe aim of this study was to investigate the expression level of GDP 11 in plasma and lung mesenchymal cells of COPD patients,and the expression of GDP 11 and p-AKT in human lung mesenchymal cells under the action of cigarette extracts.By establishing a smoke-induced rat COPD model,the relationship between GDP 11 expression level and AKT signaling pathway in lung mesenchymal cells was examined,and combined with the interference GDP 11 experiment of lung mesenchymal cells,the potential role of GDP 11 in COPD and its molecular regulation mechanism were discussed.Research methods(1)Western blot analysis was used to determine the expression level of GDF11 in the plasma of patients with COPD and blank healthy persons.(2)Western blot analysis was used to determine the expression level of the regulatory factor GDF11 in the lung mesenchymal cells of COPD patients under the action of tobacco extract.(3)The extract of cigarettes was applied to lung mesenchymal cells and the expression levels of the regulatory factors Serine/threonine Kinase(AKT),p-AKT and GDF11 in lung mesenchymal cells were detected by Real-time PCR and Western blot.(4)The rat COPD model was constructed by cigarette smoke.The expression level of GDF11,FEV1/FVC values and the correlation between GDF11 and p-AKT were examined in vivo and in vitro.Research results(1)The expression of GDF11 in COPD patients was found to be low-level expression in plasma and lung mesenchymal cells,and the level of expression was positively correlated with FEV1/FVC values.(2)It was found that CSE could reduce the expression level of GDF11 in lung mesenchymal cells,and increased the expression of intracellular p-AKT,which regulated the expression of GDF11 by activating AKT signaling pathway.(3)Decreasd the expression of GDF11 would promote the development of COPD disease by activating the AKT signaling pathway in lung mesenchymal cells.ConclusionThrough the determination of the expression of GDF11 in the plasma of patients with COPD and rat COPD model,it confirmed that CSE could promote the progression of COPD disease by down-regulating the expression level of GDF11 in lung mesenchymal cells by activating the AKT signaling pathway.The results of the study might provide potential targets for the clinical diagnosis and treatment of COPD.