JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY) ›› 2015, Vol. 29 ›› Issue (5): 38-42.doi: 10.6040/j.issn.1673-3770.0.2015.143

Previous Articles     Next Articles

Effects of silencing hypoxia inducible factor-1α on the expression of cytokines in cultured human nasal epithelial cells

LI Yingying, ZHOU Han, ZHANG Weiqiang, DONG Weida   

  1. Department of Otorhinolaryngology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Provence Hospital, Nanjing 210029, Jiangsu, China
  • Received:2015-04-07 Revised:2015-07-09 Online:2015-10-16 Published:2015-10-16

Abstract: Objective To investigate the effects of silencing hypoxia inducible factor-1α(HIF-1α) by transfecting short hairpin RNA(shRNA)into cultured human nasal epithelial cells (HNECs) and its further regulations on vascular endothelial growth factor(VEGF), transforming growth factor(TGF)β1 and basic fibroblast growth factor(bFGF). Methods HNECs were isolated from 10 inferior turbinate-cutting patients'mucosa. Two HIF-shRNA fragments were built and the best silencing shRNA sequence was used for transfection. We separated cells into three groups: the blank group, the negative control group and the ad-HIFshRNA interference group. The protein and gene expressions were detected by Western blotting and PCR. Results HNECs were transfected with GFP marketed adenovirus which carry the best silencing HIF-1α shRNA. The protein and mRNA expressions of HIF-1α were significantly reduced 40% and 39%(q=31.469, 16.590), and following, the protein and mRNA expressions of VEGF, TGF-β1 and bFGF were reduced (P<0.05). Conclusion Transfection of ad-HIFshRNA can effectively silence the expression of HIF-1α gene and protein and furthermore inhibit the expressions of VEGF, TGF-β1 and FGF-2, which suggests HIF-1α regulates the expression of VEGF, bFGF and TGF-β1 through direct or indirect ways. Thus silencing HIF-1α may provide a new way towards allergic rhiniti's treatment.

Key words: Nasal epithilial cells, RNA interference, Hypoxia-inducible factor-1α, Transforming growth factor-β1, Vascular endothelial growth factor, Basic fibroblast growth factor

CLC Number: 

  • R765.2
[1] Baldea A J, Luchette F A. The role of hypoxia-inducible factor-1alpha in response to injury and hypoxia[J]. Crit Care Med, 2014, 42(10):2312-2313.
[2] Walmsley S R, Cadwallader K A, Chilvers E R. The role of HIF-1alpha in myeloid cell inflammation[J]. Trends Immunol, 2005, 26(8):434-439.
[3] Bollinger T, Gies S, Naujoks J, et al. HIF-1alpha-and hypoxia-dependent immune responses in human CD4+CD25high T cells and T helper 17 cells[J]. J Leukoc Biol, 2014, 96(2):305-312.
[4] Hirota S A, Beck P L, MacDonald J A. Targeting hypoxia-inducible factor-1 (HIF-1) signaling in therapeutics: implications for the treatment of inflammatory bowel disease[J]. Recent Pat Inflamm Allergy Drug Discov, 2009, 3(1):1-16.
[5] Sumbayev V V, Yasinska I, Oniku A E, et al. Involvement of hypoxia-inducible factor-1 in the inflammatory responses of human LAD2 mast cells and basophils[J]. PloS One,2012, 7(3):e34259.
[6] Steinke J W, Woodard C R, Borish L. Role of hypoxia in inflammatory upper airway disease[J]. Curr Opin Allergy Clin Immunol, 2008, 8(1):16-20.
[7] Sumbayev V V, Nicholas S A. Hypoxia-inducible factor 1 as one of the "signaling drivers" of Toll-like receptor-dependent and allergic inflammation[J]. Arch Immunol Ther Exp (Warsz), 2010, 58(4):287-294.
[8] 杨琳红,董震.人鼻黏膜上皮细胞HIF-1α和VEGF的表达及意义[J].临床耳鼻咽喉头颈外科杂志, 2008, 22(8):341-345.YANG Linhong, DONG Zhen. Expression and the role of HIF-la and VEGF in human nasal epithelial cells[J]. J Clin Otolaryngol Head Neck Surgery, 2008, 22(8):341-345.
[9] Kim C H, Kim J K, Kim H J, et al. Comparison of intranasal ciclesonide, oral levocetirizine,and combination treatment for allergic rhinitis[J]. Allergy Asthma Immunol Res, 2015, 7(2):158-166.
[10] Meadows A, Kaambwa B, Novielli N, et al. A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis[J]. Health Technol Assess [JP3](Winchester, England), 2013, 17(27):vi, xi-xiv, 1-322.
[11] Baay-Guzman G J, Bebenek I G, Zeidler M, et al. HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation[J]. Respirat Res,2012,13(1):60.
[12] Huerta-Yepez S, Baay-Guzman G J, Bebenek I G, et al. Hypoxia inducible factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis[J]. Allergy, 2011, 66(7):909-918.
[13] Kim S R, Lee K S, Park H S, et al.HIF-1alpha inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium[J]. Eur J Immunol, 2010, 40(10):2858-2869.
[14] Zhou H, Chen X, Zhang W M, et al.HIF-1alpha inhibition reduces nasal inflammation in a murine allergic rhinitis model[J]. PloS One, 2012, 7(11):e48618.
[15] Lee K S, Kim S R, Park S J, et al. Mast cells can mediate vascular permeability through regulation of the PI3K-HIF-1alpha-VEGF axis[J]. Am J Respirat Crit Care Med, 2008, 178(8):787-797.
[16] Mo J H, Kim J H, Lim D J, et al. The role of hypoxia-inducible factor 1alpha in allergic rhinitis[J]. Am J Rhinol Allergy, 2014, 28(2):e100-106.
[17] Park S J, Lee K S, Kim S R, et al. AMPK activation reduces vascular permeability and airway inflammation by regulating HIF/VEGFA pathway in a murine model of toluene diisocyanate-induced asthma[J]. Inflamm Res, 2012, 61(10):1069-1083.
[18] Capetandes A, Zhuang M, Haque F N, et al. Vascular endothelial growth factor is increased by human pulmonary cells stimulated with Dermatophagoides sp. extract[J]. Allergy Asthma Proc, 2007, 28(3):324-330.
[19] Kim S R, Lee K S, Lee K B, et al. Recombinant IGFBP-3 inhibits allergic lung inflammation, VEGF production, and vascular leak in a mouse model of asthma[J]. Allergy, 2012, 67(7):869-877.
[20] Ganesan P, Matsubara K, Sugawara T, et al. Marine algal carotenoids inhibit angiogenesis by down-regulating FGF-2-mediated intracellular signals in vascular endothelial cells[J]. Mol Cell Biochem, 2013, 380(1-2):1-9.
[21] Yum H Y, Cho J Y, Miller M, et al. Allergen-induced coexpression of bFGF and TGF-beta1 by macrophages in a mouse model of airway remodeling: bFGF induces macrophage TGF-beta1 expression in vitro[J]. Inter Arch Allergy Immunol, 2011, 155(1):12-22.
[1] LI Hao, LI Yanzhong, WANG Yan. Hypoxia inducible factor-1 alpha and vascular endothelial growth factor expression in the soft palate of [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2018, 32(2): 43-47.
[2] WANG Cui, YAN Xin, ZHAO Bojun. Combination of intravitreal ranibizumab with photodynamic therapy in the treatment of wet age-related macular degeneration. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2017, 31(4): 94-97.
[3] . Effects of PGMS on the expression of vascular endothelial growth factor in the rat of diabetic retinopathy. [J]. J Otolaryngol Ophthalmol Shandong Univ, 2017, 31(2): 90-95.
[4] XU Yuanteng, CHEN Ruiqing, LIN Gongbiao, FANG Xiuling, YU Shujuan, LIANG Xiaohua, ZHANG Rong. Effect of silencing PDCD4 gene on proliferation of Hep-2 cells and the expression of β-catenin by RNA interference technique. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(5): 110-114.
[5] SHAO Hongchao, GE Yanran. Effect of rh-bFGF on the level of glutamic acid in retinal tissue of rabbits with ischemia-reperfusion injury. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(3): 93-95.
[6] LI Junying. Effects of rosuvastatin combined with fenofibrate therapy on vascular endothelial function retinopathy diabetic retinopathy patients [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(5): 72-75.
[7] CHEN Xiaoling, FEI Bing, LI Xianbin, WU Hao. Construction and identification of small interfering RNA targeting silence Trop2 expression in human laryngeal carcinoma cell line HEP2 [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(3): 51-53.
[8] DU Xiangge, ZHANG Yingchun, YAN Xin, WANG Cui, ZHAO Bojun. In vitro study of the effect of Casein Kinase2 siRNA on anginogesis [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(3): 76-80.
[9] ZHANG Ying-chun, DU Xiang-ge, YAN Xin, WANG Cui, ZHAO Bo-jun. Effect of nicotine on human RPE cells and HUVECs [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(2): 74-80.
[10] MIAO Bei-ping1, ZHANG Rui-shi2, GUO Zhi-hong3, SUN Huan-ji1, MENG Qing-guo1, WANG Xiao-bin1. Correlation analysis of VEGF expression and the content of dendritic cells in nasopharyngeal carcinoma and its clinical significance [J]. J Otolaryngol Ophthalmol Shandong Univ, 2013, 27(4): 62-65.
[11] XIE Li, WEI wei. Treatment progress of diabetic macular edema [J]. J Otolaryngol Ophthalmol Shandong Univ, 2013, 27(2): 81-85.
[12] LI Li-hua, REN Ji-hao, YIN Tuan-fang, LIU Wei. Role of expressions of STAT3,VEGF and micro-vessel density in recurrence and invasiveness of juvenile [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2011, 25(6): 11-.
[13] CHEN Jin-hui, TAO Ze-zhang. Expression and clinical significance of TERT and PCNA in the tissue and cell lines of laryngeal squamaous cell carcinoma [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2011, 25(3): 5-8.
[14] XIE Lijuan1, LI Yun1, GONG Lei1, XIAO Ying2, YANG Xiaoran1. Protection of basic fibroblast growth factor on optic nerve axons in high intraocular pressure animal models [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2009, 23(6): 62-66.
[15] HAN Xuguang1,2, WU Xinyi1, QU Fei3, SUN Yan2, WANG Xu2, XU Xianghui2

Corneal neovascularization induced by suture and alkali burn in rabbits: an experimental study

Full text



No Suggested Reading articles found!