LncRNA CASC7/miR-98-5p/SIRT3轴调控慢性阻塞性肺疾病大鼠气道炎症反应和平滑肌细胞变化  

LncRNA CASC7/miR-98-5p/SIRT3 axis regulates airway inflammatory response and smooth muscle cell changes in rats with chronic obstructive pulmonary disease

作　　者：梁海梅 欧宗兴[1] 王蕾 陈忠仁 LIANG Haimei;OU Zongxing;WANG Lei;CHEN Zhongren(Department of Respiratory and Critical Care Medicine,Haikou Hospital Affiliated to Xiangya Hospital of Central South University,Haikou 570208,China)

机构地区：[1]中南大学湘雅医学院附属海口医院呼吸与危重症医学科,海口570208

出　　处：《中国免疫学杂志》2022年第2期142-148,共7页Chinese Journal of Immunology

基　　金：海南省自然科学基金面上项目(818MS136)。

摘　　要：目的:探讨LncRNA CASC7/miR-98-5p/SIRT3轴对慢性阻塞性肺疾病(COPD)大鼠气道炎症反应和支气管平滑肌细胞(BSMCs)的影响。方法:收集临床标本用于检测CASC7、miR-98-5p、SIRT3的表达。双荧光素酶报告实验用于验证CASC7/miR-98-5p、miR-98-5p/SIRT3之间的靶向关系。建立COPD大鼠模型,ELISA检测大鼠血清中炎症相关因子表达。对BSMCs进行分组转染,使用ELISA、CCK-8、流式细胞术检测细胞炎症因子的表达、增殖能力、凋亡情况。Western blot检测PI3K信号通路相关因子的表达。结果:相对于正常样本,CASC7、SIRT3在COPD中低表达,miR-98-5p高表达,且CASC7、SIRT3与miR-98-5p的表达均呈负相关(均P<0.05)。CASC7能够调控miR-98-5p/SIRT3表达并影响PI3K信号通路变化。过表达CASC7或miR-98-5p抑制剂可阻滞炎症因子分泌和BSMCs增殖,促进BSMCs凋亡,但这种效果被SIRT3敲减部分挽救(均P<0.05)。结论:CASC7能够通过调控miR-98-5p/SIRT3轴进而减少气道炎症因子分泌,抑制BSMCs的增殖,并诱导其凋亡,CASC7在COPD的进展中扮演重要角色。Objective:To investigate the effects of LncRNA CASC7/miR-98-5p/SIRT3 axis on airway inflammatory response and bronchial smooth muscle cells(BSMCs)in rats with chronic obstructive pulmonary disease(COPD).Methods:Clinical samples were collected to detect expressions of CASC7,miR-98-5p and SIRT3. Dual luciferase reporter assay was adopted to confirm the targeting relationship of CASC7/miR-98-5p,miR-98-5p/SIRT3. COPD rats model were established and ELISA was used to test expressions of inflammatory related factors in serum of rats. BSMCs were transfected and divided into different groups,ELISA,CCK-8 assay,flow cytometry were utilized to detect inflammatory factors expression,proliferation and apoptosis in each group of cells. Western blot was adopted to determine the expressions of PI3K signaling pathway related factors.Results:Compared with normal samples,CASC7 and SIRT3 expressions were decreased while miR-98-5p expression was increased in COPD,at the same time,expressions of CASC7,SIRT3 and miR-98-5p were negatively correlated(all P<0.05). CASC7 could regulate the expression of miR-98-5p/SIRT3 and subsequently affect the changes of PI3K pathway. Overexpression of CASC7 or miR-98-5p inhibitor have the ability to block the secretion of inflammatory factors and proliferation of BSMCs,as well as induce BSMCs apoptosis,but this effect could be partly saved by SIRT3 inhibition(all P<0.05).Conclusion:CASC7 could regulate miR-98-5p/SIRT3 axis and subsequently decrease the secretion of airway inflammatory factors,inhibit BSMCs proliferation as well as induce it’s apoptosis,CASC7 plays an important role in the development of COPD.

关 键 词：LncRNA CASC7 慢性阻塞性肺疾病 支气管平滑肌细胞 增殖 凋亡 

分 类 号：R563.9[医药卫生—呼吸系统]