肺纤维化是间质性肺疾病晚期的共同表现,即肺部受损后,随着炎性反应的进展,成纤维细胞反应性增生,产生大量胶原纤维,细胞外基质过度沉积,并与其他细胞因子共同作用,进而形成肺纤维化。患者治愈率低、生存期短、病死率高,给家庭及社会带来严重负担。按病因的不同,可将肺纤维化分为:(1)与职业暴露相关的肺纤维化,如矽肺;(2)与药物相关的肺纤维化;(3)与病毒感染相关的肺纤维化;(4)与结缔组织疾病相关的肺纤维化;(5)原因不明的特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)等。microRNA(miRNA)是一类内生性、长度21～25个核苷酸的小非编码RNA,miRNA通过与其靶mRNA的3′-UTR碱基配对结合,降解靶mRNA或抑制其翻译[1],从而调控转录后基因表达而起到调控细胞增殖、凋亡、分化等作用,是生物生长发育和疾病发生发展过程中必不可少的调节因子。有研究发现,miRNA在血浆及血清中稳定存在[2,3],且组织特异性较强。因此,靶向调节miRNA可成为疾病早期诊断及治疗的潜在策略,如发现miRNA与肺纤维化的发生发展密切相关。为此,笔者就miRNA在不同类型肺纤维化之间的差异表达和共同表达,以及其调控机制进行综述。
关键词
microRNA /
肺纤维化 /
表达及调控机制
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Rigoutsos I.New tricks for animal microRNAS: targeting of amino acid coding regions at conserved and nonconserved sites [J]. Cancer Res, 2009, 69(8) : 3245-3248.
[2] Chen X,Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases[J]. Cell Res, 2008,18(10): 997-1006.
[3] Mitchell P S, Parkin R K,Kroh E M,et al. Circulating microRNAs as stable blood-based markers for cancer detection[J]. Proc Natl Acad Sci USA, 2008,105(30): 10513-10518.
[4] Faxuan W. Altered microRNAs expression profiling in experimental silicosis rats[J]. Toxicol Sci, 2012, 37(6): 1207-1215.
[5] Moschos S A. Expression profiling in vivo demonstrates rapid changes in lung microRNA levels following lipopolysaccharide-induced inflammation but not in the anti-inflammatory action of glucocorticoids[J]. BMC Genomics, 2007, 8: 240.
[6] Williams A E. MicroRNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy[J]. PLoS One, 2009, 4(6): e5889.
[7] Chen C. Smad1 expression and function during mouse embryonic lung branching morphogenesis[J]. Am J Physiol Lung Cell Mol Physiol, 2005, 288(6):1033-1039.
[8] Frank D B. Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension[J]. Circ Res, 2005, 97(5): 496-504.
[9] Fan J. Regulatory effect of miR-149 on interleukin-6 expression in silica-induced pulmonary fibrosis[J]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 2014, 32(3): 161-167.
[10] Le T T. Blockade of IL-6 Trans signaling attenuates pulmonary fibrosis[J]. J Immunol, 2014, 193(7): 3755-3768.
[11] 刘义涛,王延让,王凤山,等.血清miRNA水平检测在尘肺患者早期筛查中的研究[J].中华劳动卫生职业病杂志,2013, 31 (4): 276-278.
[12] Zhou X. Sulindac has strong antifibrotic effects by suppressing STAT3-related miR-21[J]. J Cell Mol Med, 2015, 19(5): 1103-1113.
[13] Zhong X, Chung A C, Chen H Y, et al. miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes[J]. Diabetologia,2013, 56(3):663-674.
[14] Zhu H. MicroRNA-21 in scleroderma fibrosis and its function in TGF-beta-regulated fibrosis-related genes expression[J]. J Clin Immunol, 2013, 33(6): 1100-1109.
[15] Lok S S, J J Egan. Viruses and idiopathic pulmonary fibrosis[J]. Monaldi Arch Chest Dis, 2000, 55(2): 146-150.
[16] Zhao H. Fluctuating expression of microRNAs in adenovirus infected cells[J]. Virology, 2015, 478: 99-111.
[17] Cao M. MiR-23a regulates TGF-beta-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells[J]. Int J Oncol, 2012, 41(3): 869-875.
[18] Cao M. MiR-23a-mediated migration/invasion is rescued by its target, IRS-1, in non-small cell lung cancer cells[J]. J Cancer Res Clin Oncol, 2014, 140(10): 1661-1670.
[19] Dakhlallah D. Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis[J]. Am J Respir Crit Care Med, 2013, 187(4): 397-405.
[20] Robertson KD, Uzvolgyi E, Liang G. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors[J]. Nucleic Acids Res,1999,27:2291-2298.
[21] Mallick B, Z Ghosh, J Chakrabarti. MicroRNome analysis unravels the molecular basis of SARS infection in bronchoalveolar stem cells[J]. PLoS One, 2009, 4(11): e7837.
[22] Iizuka M. Induction of microRNA-214-5p in human and rodent liver fibrosis[J]. Fibrogenesis Tissue Repair, 2012, 5(1): 12.
[23] Denby L. MicroRNA-214 antagonism protects against renal fibrosis[J]. J Am Soc Nephrol, 2014, 25(1): 65-80.
[24] Iizuka M. Induction of microRNA-214-5p in human and rodent liver fibrosis[J]. Fibrogenesis Tissue Repair, 2012, 5(1): 12.
[25] Gao SY. Arsenic trioxide prevents rat pulmonary fibrosis via miR-98 overexpression[J]. Life Sci, 2014, 114(1): 20-28.
[26] King T E Jr, A Pardo, M Selman. Idiopathic pulmonary fibrosis[J]. Lancet, 2011, 378(9807): 1949-1961.
[27] Harari S,Caminati A. IPF: new insight on pathogenesis and treatment[J]. Allergy, 2010, 65(5):537-553.
[28] Li P. Serum miR-21 and miR-155 expression in idiopathic pulmonary fibrosis[J]. J Asthma, 2013, 50(9): 960-964.
[29] Milosevic J. Profibrotic role of miR-154 in pulmonary fibrosis[J]. Am J Respir Cell Mol Biol, 2012, 47(6): 879-887.
[30] Yang S. Participation of miR-200 in pulmonary fibrosis[J]. Am J Pathol, 2012, 180(2): 484-493.
[31] Liu G. miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis[J]. J Exp Med, 2010, 207(8): 1589-1597.
[32] Pandit K V. Inhibition and role of let-7d in idiopathic pulmonary fibrosis[J]. Am J Respir Crit Care Med, 2010, 182(2): 220-229.
[33] Yang S. miR-145 regulates myofibroblast differentiation and lung fibrosis[J]. Faseb j, 2013, 27(6): 2382-2391.
[34] Lino Cardenas C L. miR-199a-5p Is upregulated during fibrogenic response to tissue injury and mediates TGFbeta-induced lung fibroblast activation by targeting caveolin-1[J]. PLoS Genet, 2013, 9(2): e1003291.
[35] Liang H. The antifibrotic effects and mechanisms of microRNA-26a action in idiopathic pulmonary fibrosis[J]. Mol Ther, 2014, 22(6): 1122-1133.
[36] Liang H. Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis[J]. Cell Death Dis, 2014, 5: e1238.
[37] Liang H. Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis[J]. Cell Death Dis, 2014, 5: e1238.
[38] Xiao X. Regulation of myofibroblast differentiation by miR-424 during epithelial-to-mesenchymal transition[J]. Arch Biochem Biophys, 2015, 566: 49-57.
[39] Das S. MicroRNA-326 regulates profibrotic functions of transforming growth factor-beta in pulmonary fibrosis[J]. Am J Respir Cell Mol Biol, 2014, 50(5): 882-892.
基金
国家自然基金面上项目(81273048);天津市职业与环境危害防制重点实验室基金(WHK201203)
PDF(817 KB)
