眼表疾病中转化生长因子-■1/Smads信号通路的研究进展
王亚卉 李青松▲ 符之瑄 桂炎香 张斌
上海中医药大学附属普陀医院眼科,上海 200062
Advances in the study of transforming growth factor-β1/Smads signaling pathway in ocular surface diseases
WANG Yahui LI Qingsong▲ FU Zhixuan GUI Yanxiang ZHANG Bin
Department of Ophthalmology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
摘要 眼表疾病的发病机制复杂多样,其中角结膜细胞外基质(ECM)代谢失衡是其发病的重要原因之一。转化生长因子-β1(TGF-β1)/Smads作为调控ECM产生、转归及代谢平衡的主要信号通路,参与了本病的发生发展。本文将主要从该通路与眼表疾病的关系方面做一综述,以期为眼表疾病的治疗提供新的依据。
关键词 :
转化生长因子-&beta ,
1(TGF-&beta ,
1)/Smads信号通路 ,
眼表疾病 ,
细胞外基质
Abstract :The pathogenesis of ocular surface diseases is complex and diverse, among which the imbalance of ECM is one of the important causes. Transforming growth factor -β1 (TGF-β1)/Smads is involved in the development of the disease as a major signaling pathway regulating the production, outcome and metabolic balance of ECM. The relationship between this pathway and ocular surface diseases will be reviewed in this paper, which will provide a new basis for the treatment of ocular surface diseases.
Key words :
Transforming grouth facter-β1(TGF-β1)/Smads signaling pathway
Ocular surface disease
Extracellular matrix
基金资助: 上海市医学重点专科建设计划项目(ZK2015A20);
上海市普陀区卫生系统自主创新科研资助项目(ptkwws201703);
上海中医药大学预算内项目(18WK106);
上海市普陀区中心医院院级科研课题(2016301A)。
通讯作者:
▲通讯作者
[1] Petroll WM,Kivanany PB,Hagenasr D,et al. Corneal Fibroblast Migration Patterns During Intrastromal Wound Healing Correlate With ECM Structure and Alignment [J]. Invest Ophthalmol Vis Sci,2015,56(12):7352-7361.
[2] 黎乐平,康红花,马明洋,等.细胞外基质胶羊膜棒的生物学特性及其在雌兔干眼中的应用[J].眼科新进展,2018,38(8):709-714.
[3] Anna B,Marcin D,NikolaosGF. TGF-β signaling in fibrosis [J]. Growth Factors,2011,29(5):196-202.
[4] Xu F,Liu C,Zhou D,et al. TGF/SMAD Pathways and Its Regulation in Hepatic Fibrosis [J]. J Histochem Cytochem,2016,64(3):157-167.
[5] Macias MJ,Martinmalpartida P,Massague J. Structural determinants of Smad function in TGF-β signaling [J]. Trends Biochem Sci,2015,40(6):296-308.
[6] Mu D,Cambier S,Fjellbirkeland L,et al. The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1 [J]. J Cell Biol,2002,157(3):493-507.
[7] Budi EH,Duan D,Derrick R. Transforming Growth Factor-β Receptors and Smads:Regulatory Complexity and Functional Versatility [J]. Trends Cell Biol,2017,27(9):658-672.
[8] Yan XH,Chen YG. Smad7:not only a regulator,but also a cross-talk mediator of TGF-β signalling [J]. Biochem J,2011,434(1):1-10.
[9] Xu P,Liu J,Derynck R. Post-translational regulation of TGF-β receptor and Smad signaling [J]. Febs Lett,2012, 586(14):1871-1884.
[10] Massagu XJ. TGF-β signalling in context [J]. NatRev Mol Cell Bio,2012,13(10):616-630.
[11] Hill CS. Transcriptional Control by the SMADs [J]. CshPerspect Biol,2016,8(10):a022079.
[12] Kamato D,Burch ML,Piva TJ,et al. Transforming growth factor-β signalling:role and consequences of Smad linker region phosphorylation [J]. Cellular Signal,2013,25(10):2017-2024.
[13] Tan Y,Xu Q,Li Y,et al. Crosstalk between the p38 and TGF-β signaling pathways through TβRI,TβRII and Smad3 expression in plancental choriocarcinoma JEG-3 cells [J]. Oncol Lett,2014,8(8):1307-1311.
[14] Jeon KI,Phipps RP,Sime PJ,et al. Antifibrotic Actions of Peroxisome Proliferator-Activated Receptor γ Ligands in Corneal Fibroblasts Are Mediated by β-Catenin-Regulated Pathways [J]. Am J Pathol,2017,187(8)1660-1669.
[15] Liu L,Wu J,Geng J,et al. Geographical prevalence and risk factors for pterygium:a systematic review and meta-analysis [J]. Bmj Open,2013,3(11):e003787.
[16] Fernandes M,Sangwan VS,Bansal AK,et al. Outcome of pterygium surgery:analysis over 14 years [J]. Eye,2005, 19(11):1182-1190.
[17] Hou A,Law KP,Tin MQ,et al. In vitro secretomics study of pterygium-derived fibroblasts by iTRAQ-based quantitative proteomics strategy [J]. Exp Eye Res,2016(153):14-22.
[18] Shayegan MR,Khakzad MR,Gharaee H,et al. Evaluation of transforming growth factor-beta1 gene expression in pterygium tissue of atopic patients [J]. J Chin Assoc,2016, 79(10):565-569.
[19] 石蕊,杨乐,薛雨顺,等.转化生长因子-β1抗体对人翼状胬肉成纤维细胞增殖及TGF-β1/Smad4信号转导通路的影[J].西安交通大学学报:医学版,2015,36(1):98-101.
[20] 黄燕,李梅,胡新远,等.TGF-β1、Smad3、Snail1和FoxM1在翼状胬肉中的表达及意义[J].江苏大学学报:医学版,2017(6):504-508.
[21] Chen YY,Tsai CF,Tsai MC,et al. Anti-fibrotic effect of rosmarinic acid on inhibition of pterygium epithelial cells [J]. Int J Ophthalmol,2018,11(2):189-195.
[22] 李志杰,王嫦君.关注结膜杯状细胞在维持眼表完整性中的作用[J].中华实验眼科杂志,2017,35(2):97-101.
[23] McCauley HA,Liu CY,Attia AC,et al. TGF-beta signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium [J]. Dev,2014,141(23):4628-4839.
[24] Vanathi M,Kashyap S,Khan R,et al. Ocular surface evaluation in allogenic hematopoietic stem cell transplantation patients [J]. Eur J Ophthalmol,2014,24(5):655-666.
[25] Fuerst N,Langelier N,Massarogiordano M,et al. Tear osmolarity and dry eye symptoms in diabetics [J]. Clin Ophthalmol,2014,8:507-515.
[26] Gupta A,Monroy D,Ji Z,et al. Transforming growth factor beta-1 and beta-2 in human tear fluid [J]. Curr Eye Res,1996,15(6):605-614.
[27] Yoshino K,Garg R,Monroy D,et al. Production and secretion of transforming growth factor beta (TGF-β) by the human lacrimal gland [J]. Curr Eye Res,1996,15(6):615-624.
[28] 柯梅青,张兴儒,李青松.结膜松弛症发病与炎性因子的关系[J].国际眼科纵览,2015,39(2):130-134.
[29] 项敏泓,张兴儒,张迅轶,等.结膜松弛症泪液中细胞因子的检测[J].国际眼科杂志,2010,10(9):1702-1703.
[30] 韩竹梅,张兴儒,柯梅青,等.基质金属蛋白酶及其组织抑制剂在结膜松弛症成纤维细胞中的表达[J].中国眼耳鼻喉科杂志,2013,13(6):365-367.
[31] 项敏泓,李轶捷,张兴儒,等.杞精明目汤药物血清对结膜松弛症患者球结膜成纤维细胞中基质金属蛋白酶表达的影响[J].中华实验眼科杂志,2013,31(10):940-943.
[32] 贾元玲,项敏泓,文杭,等.杞精明目汤颗粒剂对肿瘤坏死因子-α刺激下结膜松弛症成纤维细胞MAPK信号通路的影响[J].眼科新进展,2018,38(4):319-323.
[33] Nelson EF,Huang CW,Ewel JM,et al. Halofuginone down-regulates Smad3 expression and inhibits the TGF-beta induced expression of fibrotic markers in human corneal fibroblasts [J]. Mol Vis,2012,72(4):479-487.
[34] Seet LF,Toh LZ,Finger SN,et al. Valproic acid suppresses collagen by selective regulation of Smads in conjunctival fibrosis [J]. Mol Med,2016,94(3):321-334.
[35] Gupta S,Rodier JT,Sharma A,et al. Targeted AAV5-Smad7 gene therapy inhibits corneal scarring in vivo [J]. PloS One,2017,12(3):e0172928.
[36] Jeon ES,Kim JH,Ryu H,et al. Lysophosphatidic acid activates TGFBIp expression in human corneal fibroblasts through a TGF-β1 dependent pathway [J]. Cell Signal,2012,24(6):1241-1250.
[37] Yellore VS,Rayner SA,Aldave AJ. TGFB1-Induced Extracellular Expression of TGFBIp and Inhibition of TGFBIp Expression by RNA Interference in a Human Corneal Epithelial Cell Line [J]. Invest Ophthalmol Vis Sci,2011, 52(2):757-763.
[38] Choi SI,Kim BY,Dadakhujaev S,et al. Inhibition of TGFBIp expression by lithium:implications for TGFBI-linked corneal dystrophy therapy [J]. Invest Ophthalmol Vis Sci,2011,52(6):3293-3330.
[39] Kim TI,Lee H,Hong HK,et al. Inhibitory Effect of Tranilast on Transforming Growth Factor-Beta Induced Protein in Granular Corneal Dystrophy Type 2 Corneal Fibroblasts [J]. Invest Ophthalmol Vis Sci,2015,34(8)950-958.
[40] Davidson AE,Hayes S,Hardcastle AJ,et al. The pathogenesis of keratoconus [J]. Eye,2014,28(2):189-195.
[41] Engler C,Chakravarti S,Doyle J,et al. Transforming growth factor-β signaling pathway activation in Keratoconus [J]. Am J Ophthalmol,2011,151(5):752-759.
[42] riyadarsini S,McKay TB,Karamichos D,et al. Keratoconus in vitro and the key players of the TGF-β pathway [J]. Mol Vis,2015,21:577-588.
[43] Sharif R,Hjortdal J,Sejersen H,et al. Human in Vitro Model Reveals the Effects of Collagen Cross-Linking on Keratoconus Pathogenesis [J]. Sci Rep,2017,7(1):12517.