Ruda Wei1, Liting Chen1,2, Pengchuan Li1, Chaoyang Lin3, Qingshi Zeng4. 1. Hebei North University Zhangjiakou 075000, Hebei, P. R. China. 2. Department of Cardiovascular Medicine, Air force Medical Center, PLA Beijing 100142, P. R. China. 3. Department of Internal Medicine, Dachong Hospital of Zhongshan Zhongshan 528476, Guangdong, P. R. China. 4. Department of Radiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Jinan 250011, Shandong, P. R. China.
Abstract
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by medial hypertrophy due to pulmonary artery smooth muscle cell (PASMC) hyperplasia. In the present study, we conducted bioinformatic analyses and cellular experiments to assess the involvement of the interleukin-13 (IL-13) in IPAH. METHODS: The differentially expressed genes (DEGs) in IPAH and DEGs in IPAH caused by IL-13 treatment were screened using the GEO database. PPI networks were used to analyze the hub genes. Hypoxia-induced PASMCs were treated with IL-13 for in vitro assays. CCK8 and EdU staining were used to observe proliferation of PASMCs, and RT-qPCR was applied to detect the expression of hub genes. The conserved binding sites of microRNAs (miRNAs) in the 3'UTR of hub genes were investigated, and the regulatory relationships of the relevant miRNAs on their targets were verified by RT-qPCR and dual-luciferase assays. The GO and KEGG analyses were performed to study the downstream pathways. The effect of hub genes on immune cell infiltration in IPAH was investigated. RESULTS: IL-13 altered gene expression in IPAH. IL-13 inhibited the proliferation and the expression of hub genes in PASMCs. The 3'UTR sites between HNRNPA2B1, HNRNPH1, SRSF1, HNRNPU and HNRNPA3 in the hub genes and candidate regulatory miRNAs were well conserved in humans. IL-13-mediated hub genes regulated multiple pathways and influenced immune cell infiltration. Hypoxia-induced PASMCs promoted the M2 polarization of macrophages, whereas IL-13-treated PASMCs skewed the macrophages toward M1 polarization. CONCLUSIONS: IL-13-mediated alterations in hub genes inhibit PASMC proliferation and promote M1 macrophage infiltration in IPAH. AJTR
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by medial hypertrophy due to pulmonary artery smooth muscle cell (PASMC) hyperplasia. In the present study, we conducted bioinformatic analyses and cellular experiments to assess the involvement of the interleukin-13 (IL-13) in IPAH. METHODS: The differentially expressed genes (DEGs) in IPAH and DEGs in IPAH caused by IL-13 treatment were screened using the GEO database. PPI networks were used to analyze the hub genes. Hypoxia-induced PASMCs were treated with IL-13 for in vitro assays. CCK8 and EdU staining were used to observe proliferation of PASMCs, and RT-qPCR was applied to detect the expression of hub genes. The conserved binding sites of microRNAs (miRNAs) in the 3'UTR of hub genes were investigated, and the regulatory relationships of the relevant miRNAs on their targets were verified by RT-qPCR and dual-luciferase assays. The GO and KEGG analyses were performed to study the downstream pathways. The effect of hub genes on immune cell infiltration in IPAH was investigated. RESULTS: IL-13 altered gene expression in IPAH. IL-13 inhibited the proliferation and the expression of hub genes in PASMCs. The 3'UTR sites between HNRNPA2B1, HNRNPH1, SRSF1, HNRNPU and HNRNPA3 in the hub genes and candidate regulatory miRNAs were well conserved in humans. IL-13-mediated hub genes regulated multiple pathways and influenced immune cell infiltration. Hypoxia-induced PASMCs promoted the M2 polarization of macrophages, whereas IL-13-treated PASMCs skewed the macrophages toward M1 polarization. CONCLUSIONS: IL-13-mediated alterations in hub genes inhibit PASMC proliferation and promote M1 macrophage infiltration in IPAH. AJTR
Authors: Mathias Uhlén; Linn Fagerberg; Björn M Hallström; Cecilia Lindskog; Per Oksvold; Adil Mardinoglu; Åsa Sivertsson; Caroline Kampf; Evelina Sjöstedt; Anna Asplund; IngMarie Olsson; Karolina Edlund; Emma Lundberg; Sanjay Navani; Cristina Al-Khalili Szigyarto; Jacob Odeberg; Dijana Djureinovic; Jenny Ottosson Takanen; Sophia Hober; Tove Alm; Per-Henrik Edqvist; Holger Berling; Hanna Tegel; Jan Mulder; Johan Rockberg; Peter Nilsson; Jochen M Schwenk; Marica Hamsten; Kalle von Feilitzen; Mattias Forsberg; Lukas Persson; Fredric Johansson; Martin Zwahlen; Gunnar von Heijne; Jens Nielsen; Fredrik Pontén Journal: Science Date: 2015-01-23 Impact factor: 47.728