OBJECTIVE: Recent studies were widely concerned about the role of lncRNAs in hypoxic pulmonary hypertension (HPH). HAS2 was found significantly highly expressed in HPH, but the antisense of HAS2 (HAS2-AS1) has not been explored in HPH, providing a new potential therapeutic target of HPH. METHODS: In this study, human fetal lung fibroblast-1 (HFL-1) cells were cultured under hypoxia conditions to stimulate the pathological process of HPH. Transwell and wound-healing assays were used to detect HFL-1 cell migration, and CCK 8 assay was used to detect cell proliferation. The upstream transcription factor of HAS2-AS1 was predicted by JASPAR website, and the binding site between C/EBPβ and HAS2-AS1 was predicted by JASPAR, too. In order to verify the association between C/EBPβ and the HAS2 promoter region, we used chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene detection, western blot to detect the expression of inflammation-related proteins, and qRT-PCR to detect the expression of HAS2-AS1 and HAS2. Idiopathic pulmonary fibrosis (IPF) with HPH patient microarray data was downloaded from the GEO database and analyzed by R software. RESULTS: Our study showed that HAS2-AS1 and C/EBPβ were highly expressed in hypoxic HFL-1 cells, and the knockdown of HAS2-AS1 expression could inhibit the proliferation, migration, and inflammatory response of HFL-1 cells. C/EBPβ binds to the promoter region of HAS2-AS1 and has a positive regulation effect on the transcription of HAS2-AS1. Furthermore, C/EBPβ can regulate the proliferation, migration, and inflammatory response of HFL-1 cells through HAS2-AS1. CONCLUSION: This study suggested that C/EBPβ could upregulate HAS2-AS1 expression and induce HFL-1 cell proliferation, migration, and inflammation response.
OBJECTIVE: Recent studies were widely concerned about the role of lncRNAs in hypoxic pulmonary hypertension (HPH). HAS2 was found significantly highly expressed in HPH, but the antisense of HAS2 (HAS2-AS1) has not been explored in HPH, providing a new potential therapeutic target of HPH. METHODS: In this study, human fetal lung fibroblast-1 (HFL-1) cells were cultured under hypoxia conditions to stimulate the pathological process of HPH. Transwell and wound-healing assays were used to detect HFL-1 cell migration, and CCK 8 assay was used to detect cell proliferation. The upstream transcription factor of HAS2-AS1 was predicted by JASPAR website, and the binding site between C/EBPβ and HAS2-AS1 was predicted by JASPAR, too. In order to verify the association between C/EBPβ and the HAS2 promoter region, we used chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene detection, western blot to detect the expression of inflammation-related proteins, and qRT-PCR to detect the expression of HAS2-AS1 and HAS2. Idiopathic pulmonary fibrosis (IPF) with HPH patient microarray data was downloaded from the GEO database and analyzed by R software. RESULTS: Our study showed that HAS2-AS1 and C/EBPβ were highly expressed in hypoxic HFL-1 cells, and the knockdown of HAS2-AS1 expression could inhibit the proliferation, migration, and inflammatory response of HFL-1 cells. C/EBPβ binds to the promoter region of HAS2-AS1 and has a positive regulation effect on the transcription of HAS2-AS1. Furthermore, C/EBPβ can regulate the proliferation, migration, and inflammatory response of HFL-1 cells through HAS2-AS1. CONCLUSION: This study suggested that C/EBPβ could upregulate HAS2-AS1 expression and induce HFL-1 cell proliferation, migration, and inflammation response.
Authors: Werner Seeger; Yochai Adir; Joan Albert Barberà; Hunter Champion; John Gerard Coghlan; Vincent Cottin; Teresa De Marco; Nazzareno Galiè; Stefano Ghio; Simon Gibbs; Fernando J Martinez; Marc J Semigran; Gerald Simonneau; Athol U Wells; Jean-Luc Vachiéry Journal: J Am Coll Cardiol Date: 2013-12-24 Impact factor: 24.094
Authors: Karim C El Kasmi; Steven C Pugliese; Suzette R Riddle; Jens M Poth; Aimee L Anderson; Maria G Frid; Min Li; Soni S Pullamsetti; Rajkumar Savai; Maria A Nagel; Mehdi A Fini; Brian B Graham; Rubin M Tuder; Jacob E Friedman; Holger K Eltzschig; Ronald J Sokol; Kurt R Stenmark Journal: J Immunol Date: 2014-06-13 Impact factor: 5.422
Authors: Harry Karmouty-Quintana; Tingting Weng; Luis J Garcia-Morales; Ning-Yuan Chen; Mesias Pedroza; Hongyan Zhong; Jose G Molina; Raquel Bunge; Brian A Bruckner; Yang Xia; Richard A Johnston; Matthias Loebe; Dewan Zeng; Harish Seethamraju; Luiz Belardinelli; Michael R Blackburn Journal: Am J Respir Cell Mol Biol Date: 2013-12 Impact factor: 6.914
Authors: Rubin M Tuder; Stephen L Archer; Peter Dorfmüller; Serpil C Erzurum; Christophe Guignabert; Evangelos Michelakis; Marlene Rabinovitch; Ralph Schermuly; Kurt R Stenmark; Nicholas W Morrell Journal: J Am Coll Cardiol Date: 2013-12-24 Impact factor: 24.094