留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

Primary cilia in corneal development and disease

Ting Song Jun Zhou

Ting Song, Jun Zhou. Primary cilia in corneal development and disease. Zoological Research, 2020, 41(5): 495-502. doi: 10.24272/j.issn.2095-8137.2020.109
Citation: Ting Song, Jun Zhou. Primary cilia in corneal development and disease. Zoological Research, 2020, 41(5): 495-502. doi: 10.24272/j.issn.2095-8137.2020.109

原生纤毛在角膜发育和疾病中的作用

doi: 10.24272/j.issn.2095-8137.2020.109

Primary cilia in corneal development and disease

Funds: This work was supported by the Taishan Scholars Program of Shandong Province (20161201)
More Information
  • 摘要: 角膜是位于眼球前部的透明的无血管组织,是防止外部损伤的重要屏障。角膜的上皮细胞和内皮细胞都具有原生纤毛,它们可以感知外部环境的变化并调节细胞内信号通路。越来越多的证据表明,原生纤毛以多种方式调节角膜的发育,包括参与角膜上皮分层和维持角膜内皮细胞形态。此外,原生纤毛也参与了角膜疾病的发病过程。在这篇综述中,我们讨论了原生纤毛与角膜发育近年来的报道,明确了原生纤毛在角膜发育中的关键作用。同时我们还讨论了纤毛功能异常和角膜疾病之间的联系,为靶向原生纤毛来治疗角膜疾病提供依据。
  • Figure  1.  Structures of normal and diseased corneal tissues

    The cornea is composed of an epithelial layer, stroma, endothelial layer, Bowman’s membrane, and Descemet’s membrane. The epithelial layer is formed from multiple layers of cells, but only basal layer cells can divide. The endothelial layer is a monolayer and the cells are blocked in the G0/G1 phase of the cell cycle. In the normal cornea, the epithelial layer relies on a stable multilayered structure to prevent external damage, and endothelial cells are closely arranged together with Descemet’s membrane to prevent the flow of aqueous humor to the stroma and consequent corneal edema. Keratoconus is the most common corneal epithelial disease and is characterized by protrusion of the central cornea and thinning of the epithelial layer. Some abnormally expressed cilium-related molecules have been identified in keratoconus, such as up-regulation of TGF-β1 and TIMP3 (negatively correlated with cilia) and down-regulation of VEGF, COL1A1, and COL1A2 (positively correlated with cilia). Endothelial dystrophy is the most common retinal endothelial disease, in which endothelial cells are lost in large quantities, cells expand, and Descemet’s membrane is destroyed, causing aqueous humor to flow to the stroma, leading to corneal edema. Some abnormal cilium-related molecules have also been found in endothelial dystrophy, such as down-regulated ZEB1 expression, which is positively correlated with cilia, and TCF4 mutations that affect the Wnt/β-catenin pathway.

    Figure  2.  Patterns of primary cilia during corneal development

    A: In mice, at E11, the epithelial layer begins to develop from the ectoderm; at E12.5, the epithelial layer continues to form, at which time primary cilia can be detected; at E17.5, the epithelial layer slowly develops into two layers until the mouse opens its eyelids (around P12), after which it begins to develop rapidly. By P70, the epithelial layer matures, forming a stable structure of 6−8 layers of cells. Throughout development, primary cilia only exist on basal cells. B: At E11-12.5, neural crest cells begin to migrate to form endothelial cells; at E17.5, tight junctions form between the cells. Primary cilia are not detectable throughout the embryonic period, and cell morphology is irregular. From P2 to P12, the primary cilia begin to grow, regulating hexagonal cell morphology changes; at P35, most of the primary cilia depolymerize. By P70, the primary cilia completely disappear, cells are regular hexagons, and a mature endothelial layer has developed.

  • [1] Ahn YJ, Choi SI, Yum HR, Shin SY, Park SH. 2017. Clinical features in children with posterior polymorphous corneal dystrophy. Optometry and Vision Science, 94(4): 476−481. doi:  10.1097/OPX.0000000000001039
    [2] Anvarian Z, Mykytyn K, Mukhopadhyay S, Pedersen LB, Christensen ST. 2019. Cellular signalling by primary cilia in development, organ function and disease. Nature Reviews Nephrology, 15(4): 199−219. doi:  10.1038/s41581-019-0116-9
    [3] Baek H, Shin HJ, Kim JJ, Shin N, Kim S, Yi MH, et al. 2017. Primary cilia modulate tlr4-mediated inflammatory responses in hippocampal neurons. Journal of Neuroinflammation, 14(1): 189. doi:  10.1186/s12974-017-0958-7
    [4] Berbari NF, O'Connor AK, Haycraft CJ, Yoder BK. 2009. The primary cilium as a complex signaling center. Current Biology, 19(13): R526−R535. doi:  10.1016/j.cub.2009.05.025
    [5] Blitzer AL, Panagis L, Gusella GL, Danias J, Mlodzik M, Iomini C. 2011. Primary cilia dynamics instruct tissue patterning and repair of corneal endothelium. Proceedings of the National Academy of Sciences of the United States of America, 108(7): 2819−2824. doi:  10.1073/pnas.1016702108
    [6] Bykhovskaya Y, Gromova A, Makarenkova HP, Rabinowitz YS. 2016. Abnormal regulation of extracellular matrix and adhesion molecules in corneas of patients with keratoconus. International Journal of Keratoconus and Ectatic Corneal Diseases, 5(2): 63−70. doi:  10.5005/jp-journals-10025-1123
    [7] Chaerkady R, Shao HJ, Scott SG, Pandey A, Jun AS, Chakravarti S. 2013. The keratoconus corneal proteome: Loss of epithelial integrity and stromal degeneration. Journal of Proteomics, 87: 122−131. doi:  10.1016/j.jprot.2013.05.023
    [8] Chen XM, Li YP, Hua CF, Jia PJ, Xing YP, Xue BH, et al. 2019. Establishment of rapid risk assessment model for cigarette smoke extract exposure in chronic obstructive pulmonary disease. Toxicology Letters, 316: 10−19. doi:  10.1016/j.toxlet.2019.08.020
    [9] Chen YT, Chen FY, Vijmasi T, Stephens DN, Gallup M, McNamara NA. 2013. Pax6 downregulation mediates abnormal lineage commitment of the ocular surface epithelium in aqueous-deficient dry eye disease. PLoS One, 8(10): e77286. doi:  10.1371/journal.pone.0077286
    [10] Chen ZZ, Niu YY. 2019. Stem cell therapy for parkinson's disease using non-human primate models. Zoological Research, 40(5): 349−357. doi:  10.24272/j.issn.2095-8137.2019.053
    [11] Cho YK, Zhang XH, Uehara H, Young JR, Archer B, Ambati B. 2012. Vascular endothelial growth factor receptor 1 morpholino increases graft survival in a murine penetrating keratoplasty model. Investigative Ophthalmology & Visual Science, 53(13): 8458−8471.
    [12] Chung DD, Zhang WL, Jatavallabhula K, Barrington A, Jung JY, Aldave AJ. 2019. Alterations in GRHL2-OVOL2-ZEB1 axis and aberrant activation of wnt signaling lead to altered gene transcription in posterior polymorphous corneal dystrophy. Experimental Eye Research, 188: 107696. doi:  10.1016/j.exer.2019.107696
    [13] Collin SP, Collin HB. 2004. Primary cilia in vertebrate corneal endothelial cells. Cell Biology International, 28(2): 125−130. doi:  10.1016/j.cellbi.2003.11.011
    [14] Cui XH, Hong JX, Wang F, Deng SX, Yang YJ, Zhu XY, et al. 2014. Assessment of corneal epithelial thickness in dry eye patients. Optometry and Vision Science, 91(12): 1446−1454. doi:  10.1097/OPX.0000000000000417
    [15] Cvekl A, Tamm ER. 2004. Anterior eye development and ocular mesenchyme: new insights from mouse models and human diseases. Bioessays, 26(4): 374−386. doi:  10.1002/bies.20009
    [16] Das SK, Gupta I, Cho YK, Zhang XH, Uehara H, Muddana SK, et al. 2014. Vimentin knockdown decreases corneal opacity. Investigative Ophthalmology & Visual Science, 55(7): 4030−4040.
    [17] de Paiva CS, Pflugfelder SC, Ng SM, Akpek EK. 2019. Topical cyclosporine a therapy for dry eye syndrome. Cochrane Database of Systematic Reviews, 9(9): Cd010051.
    [18] DelMonte DW, Kim T. 2011. Anatomy and physiology of the cornea. Journal of Cataract & Refractive Surgery, 37(3): 588−598.
    [19] Dinsmore C, Reiter JF. 2016. Endothelial primary cilia inhibit atherosclerosis. EMBO Reports, 17(2): 156−166. doi:  10.15252/embr.201541019
    [20] Djalilian AR, Namavari A, Ito A, Balali S, Afshar A, Lavker RM, et al. 2008. Down-regulation of notch signaling during corneal epithelial proliferation. Molecular Vision, 14: 1041−1049.
    [21] Douvaras P, Mort RL, Edwards D, Ramaesh K, Dhillon B, Morley SD, et al. 2013. Increased corneal epithelial turnover contributes to abnormal homeostasis in the pax6+/- mouse model of aniridia. PLoS One, 8(8): e71117. doi:  10.1371/journal.pone.0071117
    [22] Edelhauser HF. 2006. The balance between corneal transparency and edema: the proctor lecture. Investigative Ophthalmology & Visual Science, 47(5): 1754−1767.
    [23] Ezratty EJ, Stokes N, Chai S, Shah AS, Williams SE, Fuchs E. 2011. A role for the primary cilium in notch signaling and epidermal differentiation during skin development. Cell, 145(7): 1129−1141. doi:  10.1016/j.cell.2011.05.030
    [24] Feizi S. 2018. Corneal endothelial cell dysfunction: etiologies and management. Therapeutic Advances in Ophthalmology, 10. doi:  10.1177/2515841418815802
    [25] Grimes DT, Boswell CW, Morante NFC, Henkelman RM, Burdine RD, Ciruna B. 2016. Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature. Science, 352(6291): 1341−1344. doi:  10.1126/science.aaf6419
    [26] Grisanti L, Revenkova E, Gordon RE, Iomini C. 2016. Primary cilia maintain corneal epithelial homeostasis by regulation of the notch signaling pathway. Development, 143(12): 2160−2171. doi:  10.1242/dev.132704
    [27] Gupta R, Kumawat BL, Paliwal P, Tandon R, Sharma N, Sen S, et al. 2015. Association of ZEB1 and TCF4 rs613872 changes with late onset fuchs endothelial corneal dystrophy in patients from northern india. Molecular Vision, 21: 1252−1260.
    [28] Hafford-Tear NJ, Tsai YC, Sadan AN, Sanchez-Pintado B, Zarouchlioti C, Maher GJ, et al. 2019. CRISPR/cas9-targeted enrichment and long-read sequencing of the fuchs endothelial corneal dystrophy-associated tcf4 triplet repeat. Genetics in Medicine, 21(9): 2092−2102. doi:  10.1038/s41436-019-0453-x
    [29] Hoar RM. 1982. Embryology of the eye. Environmental Health Perspectives, 44: 31−34. doi:  10.1289/ehp.824431
    [30] Joyce NC. 2003. Proliferative capacity of the corneal endothelium. Progress in Retinal and Eye Research, 22(3): 359−389. doi:  10.1016/S1350-9462(02)00065-4
    [31] Kanellopoulos AJ. 2009. Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided prk for treatment of keratoconus. Journal of Refractive Surgery, 25(9): S812−S818. doi:  10.3928/1081597X-20090813-10
    [32] Keller J, Giralt J, Alforja S, Casaroli-Marano RP. 2015. Altering the clinical course of sorsby fundus dystrophy with the use of anti-vascular endothelial growth factor intraocular therapy. Retinal Cases and Brief Reports, 9(2): 104−105. doi:  10.1097/ICB.0000000000000103
    [33] Kopinke D, Roberson EC, Reiter JF. 2017. Ciliary hedgehog signaling restricts injury-induced adipogenesis. Cell, 170(2): 340−351. e312. doi:  10.1016/j.cell.2017.06.035
    [34] Lehman JM, Michaud EJ, Schoeb TR, Aydin-Son Y, Miller M, Yoder BK. 2008. The oak ridge polycystic kidney mouse: Modeling ciliopathies of mice and men. Developmental Dynamics, 237(8): 1960−1971. doi:  10.1002/dvdy.21515
    [35] Loukovitis E, Kozeis N, Gatzioufas Z, Kozei A, Tsotridou E, Stoila M, et al. 2019. The proteins of keratoconus: a literature review exploring their contribution to the pathophysiology of the disease. Advances in Therapy, 36(9): 2205−2222. doi:  10.1007/s12325-019-01026-0
    [36] Lu Y, Ai JZ, Gessler D, Su Q, Tran K, Zheng Q, et al. 2016. Efficient transduction of corneal stroma by adeno-associated viral serotype vectors for implications in gene therapy of corneal diseases. Human Gene Therapy, 27(8): 598−608. doi:  10.1089/hum.2015.167
    [37] Lwigale PY. 2015. Corneal development: different cells from a common progenitor. Progress in Molecular Biology and Translational Science, 134: 43−59. doi:  10.1016/bs.pmbts.2015.04.003
    [38] Lyu R, Zhou J. 2017. The multifaceted roles of primary cilia in the regulation of stem cell properties and functions. Journal of Cellular Physiology, 232(5): 935−938. doi:  10.1002/jcp.25683
    [39] Ma X, Wong ASY, Tam HY, Tsui SYK, Chung DLS, Feng B. 2018. In vivo genome editing thrives with diversified CRISPR technologies. Zoological Research, 39(2): 58−71. doi:  10.24272/j.issn.2095-8137.2017.012
    [40] Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, et al. 2007. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: Regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Human Mutation, 28(3): 209−221. doi:  10.1002/humu.20429
    [41] Maugeri G, Longo A, D'Amico AG, Rasa DM, Reibaldi M, Russo A, et al. 2018. Trophic effect of PACAP on human corneal endothelium. Peptides, 99: 20−26. doi:  10.1016/j.peptides.2017.11.003
    [42] May-Simera HL, Wan Q, Jha BS, Hartford J, Khristov V, Dejene R, et al. 2018. Primary cilium-mediated retinal pigment epithelium maturation is disrupted in ciliopathy patient cells. Cell Reports, 22(1): 189−205. doi:  10.1016/j.celrep.2017.12.038
    [43] McMonnies CW. 2015. Inflammation and keratoconus. Optometry and Vision Science, 92(2): e35−e41. doi:  10.1097/OPX.0000000000000455
    [44] Mohammadpour M, Masoumi A, Mirghorbani M, Shahraki K, Hashemi H. 2017. Updates on corneal collagen cross-linking: Indications, techniques and clinical outcomes. Journal of Current Ophthalmology, 29(4): 235−247. doi:  10.1016/j.joco.2017.07.003
    [45] Mönnich M, Borgeskov L, Breslin L, Jakobsen L, Rogowski M, Doganli C, et al. 2018. CEP128 localizes to the subdistal appendages of the mother centriole and regulates TGF-β/bmp signaling at the primary cilium. Cell Reports, 22(10): 2584−2592. doi:  10.1016/j.celrep.2018.02.043
    [46] Morishige N, Sonoda KH. 2013. Bullous keratopathy as a progressive disease: evidence from clinical and laboratory imaging studies. Cornea, 32(Suppl 1): S77−S83.
    [47] Na KS, Mok JW, Kim JY, Rho CR, Joo CK. 2012. Correlations between tear cytokines, chemokines, and soluble receptors and clinical severity of dry eye disease. Investigative Ophthalmology & Visual Science, 53(9): 5443−5450.
    [48] O'Brart DPS. 2014. Corneal collagen cross-linking: a review. Journal of Optometry, 7(3): 113−124. doi:  10.1016/j.optom.2013.12.001
    [49] Okumura N, Koizumi N, Ueno M, Sakamoto Y, Takahashi H, Hirata K, et al. 2011. Enhancement of corneal endothelium wound healing by rho-associated kinase (ROCK) inhibitor eye drops. British Journal of Ophthalmology, 95(7): 1006−1009. doi:  10.1136/bjo.2010.194571
    [50] Oliveira-Soto L, Efron N. 2001. Morphology of corneal nerves using confocal microscopy. Cornea, 20(4): 374−384. doi:  10.1097/00003226-200105000-00008
    [51] Pala R, Alomari N, Nauli SM. 2017. Primary cilium-dependent signaling mechanisms. International Journal of Molecular Sciences, 18(11): 2272. doi:  10.3390/ijms18112272
    [52] Pazour GJ, Quarmby L, Smith AO, Desai PB, Schmidts M. 2020. Cilia in cystic kidney and other diseases. Cellular Signalling, 69: 109519. doi:  10.1016/j.cellsig.2019.109519
    [53] Pitaval A, Tseng Q, Bornens M, Théry M. 2010. Cell shape and contractility regulate ciliogenesis in cell cycle-arrested cells. The Journal of Cell Biology, 191(2): 303−312. doi:  10.1083/jcb.201004003
    [54] Portal C, Rompolas P, Lwigale P, Iomini C. 2019. Primary cilia deficiency in neural crest cells models anterior segment dysgenesis in mouse. eLife, 8: e52423. doi:  10.7554/eLife.52423
    [55] Ran J, Liu M, Feng J, Li HX, Ma HX, Song T, et al. 2020. ASK1-mediated phosphorylation blocks hdac6 ubiquitination and degradation to drive the disassembly of photoreceptor connecting cilia. Developmental Cell, 53(3): 287−299. doi:  10.1016/j.devcel.2020.03.010
    [56] Reiter JF, Leroux MR. 2017. Genes and molecular pathways underpinning ciliopathies. Nature Reviews Molecular Cell Biology, 18(9): 533−547. doi:  10.1038/nrm.2017.60
    [57] Roy O, Leclerc VB, Bourget JM, Thériault M, Proulx S. 2015. Understanding the process of corneal endothelial morphological change in vitro. Investigative Ophthalmology & Visual Science, 56(2): 1228−1237.
    [58] Saghizadeh M, Chwa M, Aoki A, Lin B, Pirouzmanesh A, Brown DJ, et al. 2001. Altered expression of growth factors and cytokines in keratoconus, bullous keratopathy and diabetic human corneas. Experimental Eye Research, 73(2): 179−189. doi:  10.1006/exer.2001.1028
    [59] Sarkisian MR, Siebzehnrubl D, Hoang-Minh L, Deleyrolle L, Silver DJ, Siebzehnrubl FA, et al. 2014. Detection of primary cilia in human glioblastoma. Journal of Neuro-Oncology, 117(1): 15−24. doi:  10.1007/s11060-013-1340-y
    [60] Serrao S, Lombardo G, Cali C, Lombardo M. 2019. Role of corneal epithelial thickness mapping in the evaluation of keratoconus. Contact Lens and Anterior Eye, 42(6): 662−665. doi:  10.1016/j.clae.2019.04.019
    [61] Shen HY, Zhou Y, Zhou QJ, Li MY, Chen J. 2020. Mudskipper interleukin-34 modulates the functions of monocytes/macrophages via the colony-stimulating factor-1 receptor 1. Zoological Research, 41(2): 123−137. doi:  10.24272/j.issn.2095-8137.2020.026
    [62] Shen L, Sun P, Zhang CW, Yang L, Du LQ, Wu XY. 2017. Therapy of corneal endothelial dysfunction with corneal endothelial cell-like cells derived from skin-derived precursors. Scientific Reports, 7(1): 13400. doi:  10.1038/s41598-017-13787-1
    [63] Solinís MA, del Pozo-Rodríguez A, Apaolaza PS, Rodríguez-Gascón A. 2015. Treatment of ocular disorders by gene therapy. European Journal of Pharmaceutics and Biopharmaceutics, 95: 331−342. doi:  10.1016/j.ejpb.2014.12.022
    [64] Stolz A, Neufeld K, Ertych N, Bastians H. 2015. Wnt-mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation. EMBO Reports, 16(4): 490−499. doi:  10.15252/embr.201439410
    [65] Sun YZ, Liu ST, Li XM, Zou K. 2019. Progress in in vitro culture and gene editing of porcine spermatogonial stem cells. Zoological Research, 40(5): 343−348. doi:  10.24272/j.issn.2095-8137.2019.051
    [66] Tang H, Zhang W, Yan XM, Wang LP, Dong H, Shou T, et al. 2016. Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset fuchs corneal dystrophy. International Journal of Molecular Medicine, 37(6): 1487−1500. doi:  10.3892/ijmm.2016.2570
    [67] Torrecilla J, Del Pozo-Rodríguez A, Vicente-Pascual M, Solinís MÁ, Rodriguez-Gascon A. 2018. Targeting corneal inflammation by gene therapy: emerging strategies for keratitis. Experimental Eye Research, 176: 130−140. doi:  10.1016/j.exer.2018.07.006
    [68] Toyono T, Usui T, Villarreal G Jr, Kallay L, Matthaei M, Vianna LM, et al. 2016. Microrna-29b overexpression decreases extracellular matrix mrna and protein production in human corneal endothelial cells. Cornea, 35(11): 1466−1470. doi:  10.1097/ICO.0000000000000954
    [69] Tylkowski MA, Yang K, Hoyer-Fender S, Stoykova A. 2015. Pax6 controls centriole maturation in cortical progenitors through odf2. Cellular and Molecular Life Sciences, 72(9): 1795−1809. doi:  10.1007/s00018-014-1766-1
    [70] van Diemen FR, Kruse EM, Hooykaas MJG, Bruggeling CE, Schürch AC, van Ham PM, et al. 2016. CRISPR/cas9-mediated genome editing of herpesviruses limits productive and latent infections. PLoS Pathogens, 12(6): e1005701. doi:  10.1371/journal.ppat.1005701
    [71] Vedana G, Villarreal G Jr, Jun AS. 2016. Fuchs endothelial corneal dystrophy: current perspectives. Clinical Ophthalmology, 10: 321−330.
    [72] Wang CY, Tsai HL, Syu JS, Chen TY, Su MT. 2017. Primary cilium-regulated EG-VEGF signaling facilitates trophoblast invasion. Journal of Cellular Physiology, 232(6): 1467−1477. doi:  10.1002/jcp.25649
    [73] Wieben ED, Baratz KH, Aleff RA, Kalari KR, Tang XJ, Maguire LJ, et al. 2019. Gene expression and missplicing in the corneal endothelium of patients with a TCF4 trinucleotide repeat expansion without fuchs' endothelial corneal dystrophy. Investigative Ophthalmology & Visual Science, 60(10): 3636−3643.
    [74] Williams KA, Irani YD. 2016. Gene therapy and gene editing for the corneal dystrophies. Asia-Pacific Journal of Ophthalmology, 5(4): 312−316. doi:  10.1097/APO.0000000000000215
    [75] Wood CR, Huang KY, Diener DR, Rosenbaum JL. 2013. The cilium secretes bioactive ectosomes. Current Biology, 23(10): 906−911. doi:  10.1016/j.cub.2013.04.019
    [76] Xu Q, Liu WW, Liu XL, Otkur W, Hayashi T, Yamato M, et al. 2018. Type I collagen promotes primary cilia growth through down-regulating HDAC6-mediated autophagy in confluent mouse embryo fibroblast 3T3-L1 cells. Journal of Bioscience and Bioengineering, 125(1): 8−14. doi:  10.1016/j.jbiosc.2017.07.012
    [77] Yang J, Feng S, Yi G, Wu W, Yi R, Lu X, Xu W, Qiu H. 2016. Inhibition of RelA expression via RNA interference induces immune tolerance in a rat keratoplasty model. Molecular Immunology, 73: 88−97. doi:  10.1016/j.molimm.2016.03.014
    [78] Yang Y, Hao HJ, Wu XF, Guo S, Liu Y, Ran J, et al. 2019. Mixed-lineage leukemia protein 2 suppresses ciliary assembly by the modulation of actin dynamics and vesicle transport. Cell Discovery, 5(1): 33. doi:  10.1038/s41421-019-0100-3
    [79] Yang YF, Ran J, Liu M, Li DW, Li YY, Shi XJ, et al. 2014. CYLD mediates ciliogenesis in multiple organs by deubiquitinating Cep70 and inactivating HDAC6. Cell Research, 24(11): 1342−1353. doi:  10.1038/cr.2014.136
    [80] Yu F, Guo S, Li T, Ran J, Zhao W, Li DW, et al. 2019. Ciliary defects caused by dysregulation of O-GlcNAc modification are associated with diabetic complications. Cell Research, 29(2): 171−173. doi:  10.1038/s41422-018-0114-7
    [81] Yu F, Ran J, Zhou J. 2016. Ciliopathies: does HDAC6 represent a new therapeutic target?. Trends in Pharmacological Sciences, 37(2): 114−119. doi:  10.1016/j.tips.2015.11.002
    [82] Zhong M, Gadek TR, Bui M, Shen W, Burnier J, Barr KJ, et al. 2012. Discovery and development of potent LFA-1/ICAM-1 antagonist SAR 1118 as an ophthalmic solution for treating dry eye. ACS Medicinal Chemistry Letters, 3(3): 203−206. doi:  10.1021/ml2002482
  • [1] Ji Xiao, Rong Liu, Ce-Shi Chen.  Tree shrew (Tupaia belangeri) as a novel laboratory disease animal model, Zoological Research. doi: 10.24272/j.issn.2095-8137.2017.033
    [2] Ming SHAO, Tian-Rui XU, Ce-Shi CHEN.  The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models, Zoological Research. doi: 10.13918/j.issn.2095-8137.2016.4.191
    [3] Feng-Qin HE, Heng-Rui ZHANG.  Perinatal clomiphene citrate treatment changes sexual orientations of male mice, Zoological Research. doi: 10.11813/j.issn.0254-5853.2013.5.0487
    [4] Wei-Ye LI, Yi-Quan WANG.  Establishment of full-sib families of Branchiostoma japonicum and the relationship between early development patterns and larvae survival rates, Zoological Research. doi: 10.11813/j.issn.0254-5853.2013.5.0446
    [5] SONG Hai-Yan, LIU Zai-Qun, ZHENG Lei.  Expression of IFN-γ, IL-1α, NGF-β and TNF-α during the development of cerebellar cortex of Western Anhui white goose, Zoological Research. doi: 10.3724/SP.J.1141.2012.02211
    [6] YU Yu, SUO Lun, WU Qiang.  Protocadherin x gene cluster is required for myelination and oligodendrocyte development, Zoological Research. doi: 10.3724/SP.J.1141.2012.04362
    [7] XIA Hou-JUN, ZHANG Gao-Hong, ZHENG Yong-Tang.  Roles of Dendritic Cell in Disease Progression of AIDS Primate Models, Zoological Research. doi: 10.3724/SP.J.1141.2010.01057
    [8] ZHAO Zhi-jun, WANG Rui-rui, CAO Jing, PEI Lan-ying.  Effect of Random Food Deprivation and Refeeding on Energy Budget and Development in Mice, Zoological Research. doi: 10.3724/SP.J.1141.2009.05534
    [9] WEN Ru-shu, FANG Zhan-qiang, CHEN Wei-ting.  Effects of 17β-estradiol on Vitellogenin Inducement and Gonad Development in Male Tanichthys albonubes, Zoological Research.
    [10] WU Xin-Fu, LI Tian-Fei, WEI Jia-Ning, WANG Yi, DENG Jian-Hua, GAO Jia-He, ZHAO Li-Heng.  Temperature Effects on Development and Fecundity of Aphidius gifuensis Ashmead, Zoological Research.
    [11] ZHOU Xiao-ming, SUN Xin-de.  The Influence on The Characteristics of Frequency Tuning of Bats'inferior Collicular Neurons by Early Sound Exposure, Zoological Research.
    [12] FENG Qing, WANG Ying-xiang, LI Chong-yun.  Postnatal Growth and Development in The Intermediate Slow Loris (Nycticebus intermedius) in Captivity, Zoological Research.
    [13] ZHONG Ming-chao, HUANG Zhe.  Induced Development of Pigment Macrophage Aggregate (Pma) in Adult and Juvenile of the Freshwater Catfish Silurus asotus L., Zoological Research.
    [14] CHEN Yun-he, LI Jing-yan.  The Effect of Egf on The Regeneration of Artificially Wounded Cornea Epiderm in Rhesus Monkeys, Zoological Research.
    [15] ZHANG Da-zhong CHEN Su-qing CHEN Jian-xuan et al.HE Guang-xin FENG Wen-he.  Relations Between Disease and Trace Elements in Giant Panda Hair, Zoological Research.
    [16] YANG Chang-jiu, XIONG Yu-liang et al..  Function of Platelet Aggregation on the Human Rheumatic Heart Disease,Rheumatism,Pneumopericarditis and Hyperlipemia, Zoological Research.
    [17] ZHAI Zi-yu, KO Hong-wen et al., GONG Ming-yao.  Viral Hemorrhagic Disease of Black Carp (Mylopharyngodon piceus), Zoological Research.
    [18] ZHANG Hong-wei.  Effects of Testosterone Propionate on Endocytosis of the Surface Epithelium of Buras Fabricll in Chicks, Zoological Research.
    [19] GAO Shun-de, ZHANG Hong-wei, HUANG Zhe.  Scanning Electron Microscopy Study of the Surface Epithelium of Bursa of Fabricius in Chicken, Zoological Research.
    [20] GAO Jian.  Clinical Observations on 167 Cases Treatment of Snakebite With Chinese Traditional and Western Medicines, Zoological Research.
  • 加载中
图(2)
计量
  • 文章访问数:  361
  • HTML全文浏览量:  191
  • PDF下载量:  101
  • 被引次数: 0
出版历程
  • 收稿日期:  2020-05-06
  • 录用日期:  2020-07-17
  • 网络出版日期:  2020-08-04
  • 刊出日期:  2020-09-18

目录

    /

    返回文章
    返回