ABSTRACT
Objeetive Airway remodeling is an important pathological feature of asthma.This study is to investigate the role of microRNA-21 (miR-21) in airway remodeling in asthmatic mice.Methods A total of 16 female BALB/c mice were randomly divided into control group and asthma model group.Mice were sensitized and challenged by ovalbumin to establish a murine model of asthma.The mice in the normal control group were intraperitoneally injected with phosphate buffered saline for sensitization and given a phosphate buffered saline inhalation for the challenge.Twenty-four hours after the last aerosol inhalation,lung tissues of mice were sampled and subjectd to Western blot for testing expression of TGFβ type Ⅱ receptor,Smad7,and Collagen Type Ⅰ (COL Ⅰ) in lung tissue of mice of each group.Quantitative real-time PCR was used to test miR-21 expression in lung tissue of mice of each group.Target gene prediction software (TargetScan) was used to predict target gene of miR-21.293T cell was used to conduct dual-luciferase reporter gene assay for verification of miR-21 target gene.Results Compared with control group,asthma group had increased expression of COL Ⅰ protein and miR-21 in lung tissue (t =11.94,P ＜ 0.05;t =23.05,P ＜ 0.05).Smad7 and TGF-βR Ⅱ were target genes of miR-21.Conclusion miR-21 down-regulates Smad7,a target gene of miR-21,activates the TGFβ/Smad signaling pathway,and promotes airway remodeling,indicating that miR-21 may be a therapeutic target for the treatment of airway remodeling in asthma.
ABSTRACT
MicroRNAs are a class of small,single-stranded,highly conserved RNAs,which contributes to the regulation of growth,development,metabolism and disease.Recent studies have shown that a few microRNAs play a vital role in allergic inflammation with special focus on bronchial asthma.To investigate the regulation mechanism of microRNA-21 in the pathogenesis of asthma can help to find a safe,effective and specific therapy.In this paper,the role of miRNA-21 in the pathogenesis of asthma is reviewed.
ABSTRACT
Objective:To explore the role of lectin-like oxidized low density lipoprotein (ox-LDL) receptor(LOX1) in ox-LDL stimulating endothelial nitric oxide(NO) production. Methods: LOX1 mRNA expression was detected by reverse transcription-polymerase chain reaction(RT-PCR). The quantity of NO was detected by Enzyme-method. Results: Incubation of ox-LDL increased endothelial NO production and LOX1 mRNA expression. When HUVECs were incubated with ox-LDL as well as the inhibitor of LOX1, polyinosinic acid,the increase of NO production and LOX1mRNA expression were attenuated. Conclusion: Ox-LDL enhanced endothelial NO production in a concentration-dependent manner, and the effect of ox-LDL on endothelial NO was mediated by LOX1.
ABSTRACT
AIM:To study lipopolysaccharide (LPS)-stimulated secretion of endothelin-1 (ET-1) and adrenomedullin (Adm) from human vascular endothelial cells (HVEC) and its mechanism. METHODS:In cultured HVEC, LPS was used to stimulate ET-1 and Adm secretion from HVEC. The contents of ET-1 and Adm in medium were determined by radioimmunoassay. RESULTS:LPS stimulated secretion of ET-1 and Adm from HVEC in time-dependent and concentration-dependent manner. The ratio of secreted ET-1 to Adm was not changed compared with the control group. The increase of ET-1 could be inhibited by inhibitor of extracellular signal-regulated protein kinases (PD098059) and inhibitor of P38 kinase (SB202190)（P＜0.01）, while the increase of Adm could only be inhibited by SB202190（P＜0.05）, both had no response to inhibitor of protein kinase C (H7), inhibitor of calmodulin (W7), inhibitor of calcineurin (cyclosporin A) and inhibitor of Ca2+ (nicardipine)（P＞0.05）.CONCLUSION:ERKs and P38 signal pathways may play an important role in the secretion of ET-1 from LPS -stimulated HVEC, while only P38 kinase signal pathway is invovled in the secretion of Adm.
ABSTRACT
AIM: To study lipopolysaccharide (LPS)-stimulated secretion of endothelin-1 (ET-1) and adrenomedullin (Adm) from human vascular endothelial cells (HVEC) and its mechanism. METHODS: In cultured HVEC, LPS was used to stimulate ET-1 and Adm secretion from HVEC. The contents of ET-1 and Adm in medium were determined by radioimmunoassay. RESULTS: LPS stimulated secretion of ET-1 and Adm from HVEC in time-dependent and concentration-dependent manner. The ratio of secreted ET-1 to Adm was not changed compared with the control group. The increase of ET-1 could be inhibited by inhibitor of extracellular signal-regulated protein kinases (PD 098059 ) and inhibitor of P38 kinase (SB 202190 )( P 0.05).CONCLUSION: ERKs and P38 signal pathways may play an important role in the secretion of ET-1 from LPS -stimulated HVEC, while only P38 kinase signal pathway is invovled in the secretion of Adm.