Maiying Fan1, Jing Xu1, Qiming Xiao2, Fang Chen1, Xiaotong Han3. 1. Department of Emergency, Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University), Key Laboratory of Acute and Severe Metabolomics in Hunan Province, Changsha, 410002, China. 2. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China. 3. Department of Emergency, Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University), Key Laboratory of Acute and Severe Metabolomics in Hunan Province, Changsha, 410002, China. Electronic address: XiaotongHan_H22@163.com.
Abstract
BACKGROUND: Long noncoding RNAs (lncRNAs) have been revealed to participate in cellular biological processes in multiple diseases, including asthma. Nevertheless, the role of lncRNA TCF7 (lncTCF7) in airway smooth muscle cells (ASMCs) is still covered. METHODS: The expression of lncTCF7 and TIMMDC1 in ASMCs from 12 asthma patients and 12 healthy controls were detected using qRT-PCR. Then MTT assay, EdU assay and transwell assay were conducted respectively to assess the impact of lncTCF7 on ASMCs viability, proliferation and migration. Besides, western blotting was performed to determine the protein levels of TIMMDC1 and AKT/p-AKT. RESULTS: We discovered that lncTCF7 and TIMMDC1 were upregulated in asthma groups and lncTCF7 improved ASMCs viability/proliferation and migration. In addition, lncTCF7 regulated TIMMDC1 expression indeed and PDGF-BB treated ASMCs exhibited elevated levels of lncTCF7 and TIMMDC1. Moreover, lncTCF7 suppression diminished both the mRNA and protein levels of TIMMDC1 and markedly reduced p-AKT level which could be enhanced under TIMMDC1 overexpression. Finally, both TIMMDC1 overexpression and AKT activator could restored the inhibitory impacts of lncTCF7 silence on PDGF-BB treated ASMCs. CONCLUSION: Our study uncovered that lncTCF7 facilitated human ASMCs growth and migration via targeting TIMMDC1 thus activating AKT signaling, providing a novel possible target for asthma therapy.
BACKGROUND: Long noncoding RNAs (lncRNAs) have been revealed to participate in cellular biological processes in multiple diseases, including asthma. Nevertheless, the role of lncRNA TCF7 (lncTCF7) in airway smooth muscle cells (ASMCs) is still covered. METHODS: The expression of lncTCF7 and TIMMDC1 in ASMCs from 12 asthmapatients and 12 healthy controls were detected using qRT-PCR. Then MTT assay, EdU assay and transwell assay were conducted respectively to assess the impact of lncTCF7 on ASMCs viability, proliferation and migration. Besides, western blotting was performed to determine the protein levels of TIMMDC1 and AKT/p-AKT. RESULTS: We discovered that lncTCF7 and TIMMDC1 were upregulated in asthma groups and lncTCF7 improved ASMCs viability/proliferation and migration. In addition, lncTCF7 regulated TIMMDC1 expression indeed and PDGF-BB treated ASMCs exhibited elevated levels of lncTCF7 and TIMMDC1. Moreover, lncTCF7 suppression diminished both the mRNA and protein levels of TIMMDC1 and markedly reduced p-AKT level which could be enhanced under TIMMDC1 overexpression. Finally, both TIMMDC1 overexpression and AKT activator could restored the inhibitory impacts of lncTCF7 silence on PDGF-BB treated ASMCs. CONCLUSION: Our study uncovered that lncTCF7 facilitated humanASMCs growth and migration via targeting TIMMDC1 thus activating AKT signaling, providing a novel possible target for asthma therapy.
Authors: Bonnie H Y Yeung; Jessie Huang; Steven S An; Julian Solway; Wayne Mitzner; Wan-Yee Tang Journal: Am J Respir Cell Mol Biol Date: 2020-07 Impact factor: 7.748
Authors: Dinesh Devadoss; Grant Daly; Marko Manevski; Dominika Houserova; Shah S Hussain; Nathalie Baumlin; Matthias Salathe; Glen M Borchert; Raymond J Langley; Hitendra S Chand Journal: Mucosal Immunol Date: 2020-10-29 Impact factor: 7.313