Sihui Zhao1, Yunfang Ning1, Na Qin1, Nan Ping1, Yong Yu2, Guoyan Yin3. 1. Department of Pediatrics, Heping Hospital Affiliated to Changzhi Medical College, No. 110, Yanan Sourth Road, Changzhi, 046000, Shanxi Province, China. 2. Department of Infectious Diseases, Heping Hospital Affiliated to Changzhi Medical College, Shanxi, China. 3. Department of Pediatrics, Heping Hospital Affiliated to Changzhi Medical College, No. 110, Yanan Sourth Road, Changzhi, 046000, Shanxi Province, China. hpyyekzsh@163.com.
Abstract
BACKGROUND: Asthma is a serious respiratory disease that affects the physical and mental health of children. Airway epithelial apoptosis concomitantly mediated by transforming growth factor-β1 (TGF-β1) is a crucial component of asthma pathogenesis. LncRNA growth Arrest Specific 5 (GAS5), microRNA-217 (miR-217) and Histone deacetylase 4 (HDAC4) shown a close relationship with TGF-β1-induced injury of airway epithelial. However, the mechanism underlying TGF-β1-induced injury of airway epithelial in asthma still needs to be investigated. OBJECTIVE: We aimed to investigate the effect and underlying mechanism of GAS5/miR-217/HDAC4 axis in TGF-β1-stimulated bronchial epithelial cells. METHODS: The levels of were detected by quantitative real-time polymerase chain reaction (RT-qPCR). All protein levels were determined by western blot. Cell viability and apoptosis rate were assessed by Methyl thiazolyl tetrazolium (MTT) and Flow cytometry, respectively. The targeting relationship between miR-217 and GAS5 or HDAC4 was examined with dual-luciferase reporter assay. RESULTS: TGF-β1, GAS5, HDAC4 were up-regulated, while miR-217 was down-regulated in bronchial mucosal tissues of asthmatic children and TGF-β1-treated BEAS-2B cells. TGF-β1 could reduce cell viability and induce apoptosis, while these effects could be reversed by downregulation of GAS5 or HDAC4. Mechanically, GAS5 acted as a sponge for miR-217 to regulate the expression of HDAC4. Furthermore, overexpression of HDAC4 rescued the effects of GAS5 knockdown on viability and apoptosis of TGF-β1-induced BEAS-2B cells. GAS5 knockdown induced cell viability and hampered cell apoptosis in TGF-β1-stimulated BEAS-2B cells by regulating the miR-217/HDAC4 axis. CONCLUSIONS: The lncRNA GAS5/miR-217/HDAC4 axis played an important role in regulating TGF-β1-induced bronchial epithelial cells injury, thus contributing to asthma.
BACKGROUND: Asthma is a serious respiratory disease that affects the physical and mental health of children. Airway epithelial apoptosis concomitantly mediated by transforming growth factor-β1 (TGF-β1) is a crucial component of asthma pathogenesis. LncRNA growth Arrest Specific 5 (GAS5), microRNA-217 (miR-217) and Histone deacetylase 4 (HDAC4) shown a close relationship with TGF-β1-induced injury of airway epithelial. However, the mechanism underlying TGF-β1-induced injury of airway epithelial in asthma still needs to be investigated. OBJECTIVE: We aimed to investigate the effect and underlying mechanism of GAS5/miR-217/HDAC4 axis in TGF-β1-stimulated bronchial epithelial cells. METHODS: The levels of were detected by quantitative real-time polymerase chain reaction (RT-qPCR). All protein levels were determined by western blot. Cell viability and apoptosis rate were assessed by Methyl thiazolyl tetrazolium (MTT) and Flow cytometry, respectively. The targeting relationship between miR-217 and GAS5 or HDAC4 was examined with dual-luciferase reporter assay. RESULTS: TGF-β1, GAS5, HDAC4 were up-regulated, while miR-217 was down-regulated in bronchial mucosal tissues of asthmatic children and TGF-β1-treated BEAS-2B cells. TGF-β1 could reduce cell viability and induce apoptosis, while these effects could be reversed by downregulation of GAS5 or HDAC4. Mechanically, GAS5 acted as a sponge for miR-217 to regulate the expression of HDAC4. Furthermore, overexpression of HDAC4 rescued the effects of GAS5 knockdown on viability and apoptosis of TGF-β1-induced BEAS-2B cells. GAS5 knockdown induced cell viability and hampered cell apoptosis in TGF-β1-stimulated BEAS-2B cells by regulating the miR-217/HDAC4 axis. CONCLUSIONS: The lncRNA GAS5/miR-217/HDAC4 axis played an important role in regulating TGF-β1-induced bronchial epithelial cells injury, thus contributing to asthma.