肾脏纤毛病的研究进展
Advances in the Study of the Renal Ciliopathies
DOI: 10.12677/ACM.2023.1351067, PDF,   
作者: 徐子晴, 王 墨*：重庆医科大学附属儿童医院肾内科，儿童发育疾病研究教育部重点实验室，国家儿童健康与疾病临床医学研究中心，儿童发育重大疾病国家国际科技合作基地，重庆；儿科学重庆市重点实验室，重庆
关键词: 初级纤毛；肾脏纤毛病；常染色体显性多囊肾病(ADPKD)；常染色体隐形多囊肾(ARPKD)；肾单位肾痨(NPHP)；NPHP相关性纤毛病(NPHP-RC)；眼脑肾综合征(OCRL)；Primary Cilia； Renal Ciliopathies； ADPKD； ARPKD； NPHP； NPHP-RC； OCRL
摘要: 初级纤毛是一种微管结构，作为特殊的感觉细胞器从细胞表面突出并固定在细胞骨架上。肾脏的初级纤毛是肾脏细胞的机械感受器，初级纤毛的功能受损则会引起囊肿的形成，进而导致各种肾脏疾病的发生。由于囊性肾损伤和全身炎症，肾脏纤毛病常进展至肾功能衰竭而需要肾脏替代治疗。目前肾脏纤毛病相关致病基因的具体发病机制尚未完全阐明，本综述主要总结肾脏纤毛病各个病种的临床特点、致病基因、发病机制及诊断治疗等方面的研究进展。
Abstract: Primary cilia are microtubule structures that protrude from the cell surface as specialized sensory organelles and are anchored to the cytoskeleton. The primary cilia of the kidney are mechanore-ceptors of the kidney cells, and the impairment of the function of the primary cilia will lead to the formation of cysts, which will lead to the occurrence of various kidney diseases. Renal ciliopathies often progress to renal failure and require renal replacement due to cystic kidney injury and sys-temic inflammation. At present, the specific pathogenesis of pathogenic genes related to renal cili-opathies has not been fully elucidated. This review mainly summarizes the clinical characteristics, pathogenic genes, pathogenesis, diagnosis and treatment of each disease of renal ciliopathies.
文章引用：徐子晴, 王墨. 肾脏纤毛病的研究进展[J]. 临床医学进展, 2023, 13(5): 7637-7644. https://doi.org/10.12677/ACM.2023.1351067

参考文献

[1] Huang, S., Hirota, Y. and Sawamoto, K. (2009) Various Facets of Vertebrate Cilia: Motility, Signaling, and Role in Adult Neurogenesis. Proceedings of the Japan Academy, Series B, 85, 324-336. [Google Scholar] [CrossRef] [PubMed]
[2] McConnachie, D.J., Stow, J.L. and Mallett, A.J. (2021) Ciliopathies and the Kidney: A Review. American Journal of Kidney Diseases, 77, 410-419. [Google Scholar] [CrossRef] [PubMed]
[3] Devlin, L.A. and Sayer, J.A. (2019) Renal Ciliopathies. Current Opinion in Genetics & Development, 56, 49-60. [Google Scholar] [CrossRef] [PubMed]
[4] Adamiok-Ostrowska, A. and Piekiełko-Witkowska, A. (2020) Cili-ary Genes in Renal Cystic Diseases. Cells, 9, Article No. 907. [Google Scholar] [CrossRef] [PubMed]
[5] Miceli, C., Roccio, F., Penalva-Mousset, L., Burtin, M., Leroy, C., Nemazanyy, I., Kuperwasser, N., Pontoglio, M., Friedlander, G., Morel, E., Terzi, F., Codogno, P. and Dupont, N. (2020) The Primary Cilium and Lipophagy Translate Mechanical Forces to Direct Metabolic Adaptation of Kidney Epithelial Cells. Nature Cell Biology, 22, 1091-1102. [Google Scholar] [CrossRef] [PubMed]
[6] Joly, D., Hummel, A., Ruello, A. and Knebelmann, B. (2003) Ciliary Function of Polycystins: A New Model for Cystogenesis. Nephrology Dialysis Transplantation, 18, 1689-1692. [Google Scholar] [CrossRef] [PubMed]
[7] Bergmann, C., Guay-Woodford, L.M., Harris, P.C., Horie, S., Peters, D.J.M. and Torres, V.E. (2018) Polycystic Kidney Disease. Nature Reviews Disease Primers, 4, Article No. 50. [Google Scholar] [CrossRef] [PubMed]
[8] Ma, M. (2021) Cilia and Polycystic Kidney Disease. Seminars in Cell & Developmental Biology, 110, 139-148. [Google Scholar] [CrossRef] [PubMed]
[9] Barroso-Gil, M., Olinger, E. and Sayer, J.A. (2021) Molecular Genetics of Renal Ciliopathies. Biochemical Society Transactions, 49, 1205-1220. [Google Scholar] [CrossRef] 
[10] Iliuta, I.-A., Kalatharan, V., Wang, K., Cornec-Le Gall, E., Conklin, J., Pourafkari, M., Ting, R., Chen, C., Borgo, A.C., He, N., Song, X., Heyer, C.M., Senum, S.R., Hwang, Y.H., Paterson, A.D., Harris, P.C., Khalili, K. and Pei, Y. (2017) Polycystic Kidney Disease without an Apparent Family History. Jour-nal of the American Society of Nephrology, 28, 2768-2776. [Google Scholar] [CrossRef] 
[11] Chang, A.R., Moore, B.S., Luo, J.Z., Sartori, G., Fang, B., Jacobs, S., Abdalla, Y., Taher, M., Carey, D.J., Triffo, W.J., Singh, G. and Mirshahi, T. (2022) Exome Sequencing of a Clinical Population for Autosomal Dominant Polycystic Kidney Disease. JAMA, 328, 2412-2421. [Google Scholar] [CrossRef] [PubMed]
[12] Du, N., Dong, D., Sun, L., Che, L., Li, X., Liu, Y. and Wang, B. (2021) Identification of ACOT13 and PTGER2 as Novel Candidate Genes of Autosomal Dominant Polycystic Kidney Disease through Whole Exome Sequencing. European Journal of Medical Research, 26, Article No. 142. [Google Scholar] [CrossRef] [PubMed]
[13] 沈旭峰, 徐雨辰, 孟佳林, 李奥, 樊松, 郝宗耀, 吴冠青, 梁朝朝. 常染色体隐性遗传性多囊肾病发病机制的研究进展[J]. 中华儿科杂志, 2018, 56(2): 157-160.
[14] Kim, I., Li, C., Liang, D., Chen, X.-Z., Coffy, R.J., Ma, J., Zhao, P. and Wu, G. (2008) Polycystin-2 Expression Is Regulated by a PC2-binding Domain in the Intracellular Portion of Fibrocystin. Journal of Biological Chemistry, 283, 31559-31566. [Google Scholar] [CrossRef] 
[15] Nagano, J., Kitamura, K., Hujer, K.M., Ward, C.J., Bram, R.J., Hopfer, U., Tomita, K., Huang, C. and Miller, R.T. (2005) Fibrocystin Interacts with CAML, a Protein Involved in Ca2+ Signaling. Biochemical and Biophysical Research Communications, 338, 880-889. [Google Scholar] [CrossRef] [PubMed]
[16] Lu, H., Galeano, M., Ott, E., Kaeslin, G., Kausalya, P.J., Kramer, C., Ortiz-Brüchle, N., Hilger, N., Metzis, V., Hiersche, M., Tay, S.Y., Tunningley, R., Vij, S., Courtney, A.D., Whittle, B., Wühl, E., Vester, U., Hartleben, B., Neuber, S., Frank, V., Little, M.H., Epting, D., Papathanasiou, P., Perkins, A.C., Wright, G.D., Hunziker, W., Gee, H.Y., Otto, E.A., Zerres, K., Hildebrandt, F., Roy, S., Wicking, C. and Bergmann, C. (2017) Mutations in DZIP1L, Which Encodes a Ciliary-Transition-Zone Protein, Cause Autosomal Recessive Polycystic Kidney Disease. Nature Genetics, 49, 1025-1034. [Google Scholar] [CrossRef] [PubMed]
[17] Wolf, M.T.F. (2015) Nephronophthisis and Related Syndromes. Current Opinion in Pediatrics, 27, 201-211. [Google Scholar] [CrossRef] 
[18] Hildebrandt, F. and Zhou, W. (2007) Nephronoph-thisis-Associated Ciliopathies. Journal of the American Society of Nephrology, 18, 1855-1871. [Google Scholar] [CrossRef] 
[19] Hildebrandt, F., Benzing, T. and Katsanis, N. (2021) Ciliopathies. New England Journal of Medicine, 364, 1533-1543. [Google Scholar] [CrossRef] 
[20] Tsang, S.H., Aycinena, A.R.P. and Sharma, T. (2018) Ciliopathy: Bardet-Biedl Syndrome. In: Tsang, S. and Sharma, T., Eds., Atlas of Inherited Retinal Diseases. Advances in Experi-mental Medicine and Biology, Vol. 1085, Springer, Cham, 171-174. [Google Scholar] [CrossRef] [PubMed]
[21] 戴阳丽, 罗小平, 巩纯秀, 邱正庆, 熊晖, 杨艳玲, 邹朝春. 中国儿童Bardet-Biedl综合征诊治专家共识[J]. 中国实用儿科杂志, 2022, 37(4): 241-247. [Google Scholar] [CrossRef] 
[22] Yıldız Bölükbaşı, E., Mumtaz, S., Afzal, M., Woehlbier, U., Malik, S. and Tolun, A. (2018) Homozygous Mutation in CEP19, a Gene Mutated in Morbid Obesity, in Bardet-Biedl Syn-drome with Predominant Postaxial Polydactyly. Journal of Medical Genetics, 55, 189-197. [Google Scholar] [CrossRef] [PubMed]
[23] Devi, A.R.R., Naushad, S.M. and Lingappa, L. (2020) Clini-cal and Molecular Diagnosis of Joubert Syndrome and Related Disorders. Pediatric Neurology, 106, 43-49. [Google Scholar] [CrossRef] [PubMed]
[24] Maria, B.L., Boltshauser, E., Palmer, S.C. and Tran, T.X. (1999) Clinical Features and Revised Diagnostic Criteria in Joubert Syndrome. Journal of Child Neurology, 14, 583-590. [Google Scholar] [CrossRef] [PubMed]
[25] Romani, M., Micalizzi, A. and Valente, E.M. (2013) Joubert Syndrome: Congenital Cerebellar Ataxia with the Molar Tooth. The Lancet Neurology, 12, 894-905. [Google Scholar] [CrossRef] 
[26] 林娇. 儿童肾脏纤毛相关单基因遗传病的临床及遗传学研究[D]: [硕士学位论文]. 杭州: 浙江大学, 2021.[CrossRef] 
[27] Hemachandar, R. (2014) Senior-Loken Syndrome—A Ciliopathy. Journal of Clinical and Diagnostic Research, 8, 4-5. [Google Scholar] [CrossRef] 
[28] Tsang, S.H., Aycinena, A.R.P. and Sharma, T. (2018) Ciliop-athy: Senior-Løken Syndrome. In: Tsang, S. and Sharma, T., Eds., Atlas of Inherited Retinal Diseases. Advances in Ex-perimental Medicine and Biology, Vol. 1085, Springer, Cham, 175-178. [Google Scholar] [CrossRef] [PubMed]
[29] Hartill, V., Szymanska, K., Sharif, S.M., Wheway, G. and Johnson, C.A. (2017) Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Ad-vances. Frontiers in Pediatrics, 5, Article 244. [Google Scholar] [CrossRef] [PubMed]
[30] Salonen, R., Opitz, J.M. and Reynolds, J.F. (1984) The Meckel Syndrome: Clinicopathological Findings in 67 Patients. American Journal of Medical Genetics, 18, 671-89. [Google Scholar] [CrossRef] [PubMed]
[31] Bökenkamp, A. and Ludwig, M. (2016) The Oculocerebrorenal Syndrome of Lowe: An Update. Pediatric Nephrology, 31, 2201-2212. [Google Scholar] [CrossRef] [PubMed]
[32] 张昀, 于晓晓, 刘华卫, 杨杰. Lowe综合征1例报告并文献复习[J]. 山东医药, 2016, 56(34): 73-75.
[33] Hichri, H., Rendu, J., Monnier, N., Coutton, C., Dorseuil, O., Poussou, R.V., Baujat, G., Blanchard, A., Nobili, F., Ranchin, B., Remesy, M., Salomon, R., Satre, V. and Lunardi, J. (2011) From Lowe Syndrome to Dent Disease: Correlations between Mutations of the OCRL1 Gene and Clinical and Biochem-ical Phenotypes. Human Mutation, 32, 379-388. [Google Scholar] [CrossRef] [PubMed]
[34] Luo, N., West, C.C., Murga-Zamalloa, C.A., Sun, L., Anderson, R.M., Wells, C.D., Weinreb, R.N., Travers, J.B., Khanna, H. and Sun, Y. (2012) OCRL Localizes to the Primary Cilium: A New Role for Cilia in Lowe Syndrome. Human Molecular Genetics, 21, 3333-3344. [Google Scholar] [CrossRef] [PubMed]
[35] De Matteis, M.A., Staiano, L., Emma, F. and Devuyst, O. (2017) The 5-Phosphatase OCRL in Lowe Syndrome and Dent Disease 2. Nature Reviews Nephrology, 13, 455-470. [Google Scholar] [CrossRef] [PubMed]
[36] Chebib, F.T., Perrone, R.D., Chapman, A.B., Dahl, N.K., Harris, P.C., Mrug, M., Mustafa, R.A., Rastogi, A., Watnick, T., Yu, A.S.L. and Torres, V.E. (2018) A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. Journal of the American Society of Nephrology, 29, 2458-2470. [Google Scholar] [CrossRef] 
[37] Perico, N., Antiga, L., Caroli, A., Ruggenenti, P., Fasolini, G., Ca-faro, M., Ondei, P., Rubis, N., Diadei, O., Gherardi, G., Prandini, S., Panozo, A., Bravo, R.F., Carminati, S., De Leon, F.R., Gaspari, F., Cortinovis, M., Motterlini, N., Ene-Iordache, B., Remuzzi, A. and Remuzzi, G. (2010) Sirolimus Therapy to Halt the Progression of ADPKD. Journal of the American Society of Nephrology, 21, 1031-1040. [Google Scholar] [CrossRef] 
[38] Meijer, L., Nelson, D.J., Riazanski, V., Gabdoulkhakova, A.G., Hery-Arnaud, G., Le Berre, R., Loaëc, N., Oumata, N., Galons, H., Nowak, E., Gueganton, L., Dorothée, G., Prochaz-kova, M., Hall, B., Kulkarni, A.B., Gray, R.D., Rossi, A.G., Witko-Sarsat, V., Norez, C., Becq, F., Ravel, D., Mottier, D. and Rault, G. (2016) Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis. Journal of Innate Immunity, 8, 330-349. [Google Scholar] [CrossRef] [PubMed]
[39] Kim, Y.J., Kim, S., Jung, Y., Jung, E., Kwon, H.J. and Kim, J. (2018) Eupatilin Rescues Ciliary Transition Zone Defects to Ameliorate Ciliopathy-Related Phenotypes. Journal of Clinical Investigation, 128, 3642-3648. [Google Scholar] [CrossRef] 
[40] Stokman, M.F., Saunier, S. and Benmerah, A. (2021) Renal Ciliopathies: Sorting out Therapeutic Approaches for Nephronophthisis. Frontiers in Cell and Developmental Biology, 9, Article 653138. [Google Scholar] [CrossRef] [PubMed]

为你推荐