肾纤维化Wnt/β-Catenin、Hedgehog、Klotho信号通路的最新研究进展
Recent Advances in Wnt/β-Catenin, Hedgehog and Klotho Signaling Pathways in Renal Fibrosis
DOI: 10.12677/ACM.2022.12111565, PDF,   
作者: 鲍 苗*, 呼延逸然, 鲁滟新:西安医学院,陕西 西安;陕西省人民医院肾病血透中心,陕西 西安;朱燕亭, 李振江#:陕西省人民医院肾病血透中心,陕西 西安
关键词: 肾纤维化慢性肾脏病信号通路Renal Interstitial Fibrosis Chronic Kidney Disease Signaling Pathways
摘要: 肾纤维化是指肾脏在各种原发或继发因素下导致其功能损伤、结构改变,逐渐出现肾小球、血管及间质纤维基质沉积增加,最终导致慢性肾脏病(chronic kidney disease, CKD)及终末肾衰竭。为了给纤维化诊治提供新的理论依据,作者就肾纤维化信号通路及其最新致病机制进行综述。
Abstract: Renal fibrosis refers to the kidney in a variety of primary or secondary factors leading to functional damage, structural changes, the gradual increase in glomerular, vascular and interstitial deposition of fibrous matrix, the result is chronic kidney disease (CKD) and end-stage chronic kidney disease failure. In order to provide a new theoretical basis for the diagnosis and treatment of renal fibrosis, the author reviews the signal pathway of renal fibrosis and its latest pathogenesis.
文章引用:鲍苗, 呼延逸然, 鲁滟新, 朱燕亭, 李振江. 肾纤维化Wnt/β-Catenin、Hedgehog、Klotho信号通路的最新研究进展[J]. 临床医学进展, 2022, 12(11): 10870-10877. https://doi.org/10.12677/ACM.2022.12111565

参考文献

[1] 霍明真, 李长红. 慢性肾脏病患者FGF23与PTH及血钙、血磷的关系[J]. 齐齐哈尔医学院学报, 2020, 41(2): 145-147.
[2] 王善志, 朱永俊, 唐文庄, 等. 中国成人及老年人群慢性肾脏病患病率Meta分析[J]. 中国老年学杂志, 2017, 37(21): 5384-5388.
[3] 杨舒贺, 康晓明, 孟庆云, 等. 福辛普利对UUO大鼠肾纤维化组织中Klotho蛋白、Wnt/β-catenin通路及MMP7表达的影响[J]. 黑龙江医药科学, 2019, 42(1): 6-8.
[4] 曾庆敏, 李均. Wnt和Notch信号通路在肾纤维化中的作用研究进展[J]. 中国中西医结合肾病杂志, 2019, 20(12): 1124-1126.
[5] Liu, I., Xiao, Q., Xiao, J.N., et al. (2022) Wnt/β-Catenin Signalling: Function, Biological Mechanisms, and Therapeutic Opportunities. Signal Transduction and Targeted Therapy, 7, Article No. 3. [Google Scholar] [CrossRef] [PubMed]
[6] Li, S.-S., Sun, Q., Hua, M.-R., et al. (2021) Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis. Frontiers in Pharmacology, 12, Article ID: 719880. [Google Scholar] [CrossRef] [PubMed]
[7] 肖争. β连环蛋白翻译后修饰与肾间质纤维化[J]. 肾脏病与透析肾移植杂志, 2016, 25(3): 269-273.
[8] Yu, J.E., Kim, S.-O., Hwang, J.-A., et al. (2021) Phosphorylation of β-Catenin Ser60 by Polo-Like Kinase 1 Drives the Completion of Cytokinesis. EMBO Reports, 22, e51503. [Google Scholar] [CrossRef] [PubMed]
[9] 谢莹, 宋泽庆, 王亚红, 等. LRP5蛋白在纤维化疾病中的作用及机制研究进展[J]. 海南医学, 2022, 33(13): 1727-1731.
[10] Colozza, G. and Koo, B. (2021) Wnt β-Catenin Signaling: Structure, Assembly and Endocytosis of the Signalosome. Development, Growth & Differentiation, 63, 199-218. [Google Scholar] [CrossRef] [PubMed]
[11] Acebron, S.P. and Niehrs, C. (2016) β-Catenin-Independent Roles of Wnt/LRP6 Signaling. Trends in Cell Biology, 26, 956-967. [Google Scholar] [CrossRef] [PubMed]
[12] Schunk, S.J., Floege, J., Fliser, D., et al. (2021) WNT-β-Catenin Signalling—A Versatile Player in Kidney Injury and Repair. Nature Reviews Nephrology, 11, 172-184. [Google Scholar] [CrossRef] [PubMed]
[13] Feng, Y.-L., Chen, D.-Q., Vaziri, N.D., et al. (2020) Small Molecule Inhibitors of Epithelial-Mesenchymal Transition for the Treatment of Cancer and Fibrosis. Medicinal Research Reviews, 40, 54-78. [Google Scholar] [CrossRef] [PubMed]
[14] Chen, F.T., Chen, L., Li, D., et al. (2022) Relaxin Inhibits Renal Fibrosis and the Epithelial-to-Mesenchymal Transition via the Wnt/β-Catenin Signaling Pathway. Renal Failure, 44, 513-524. [Google Scholar] [CrossRef
[15] Lee, E.-J., et al. (2020) Dickkopf-3 in Human Malignant Tumours: A Clinical Viewpoint. Anticancer Research, 40, 5969-5979. [Google Scholar] [CrossRef] [PubMed]
[16] Gröne, E.F., Federico, G., Nelson, P.J., et al. (2017) The Hormetic Functions of Wnt Pathways in Tubular Injury. Pflügers Archiv, 469, 899-906. [Google Scholar] [CrossRef] [PubMed]
[17] Zhou, D., Tan, R.J., Fu, H.Y., et al. (2016) Wnt/β-Catenin Signaling in Kidney Injury and Repair: A Double-Edged Sword. Laboratory Investigation; a Journal of Technical Methods and Pathology, 96, 156-167. [Google Scholar] [CrossRef] [PubMed]
[18] Federico, G., Meister, M., Mathow, D., et al. (2016) Tubular Dickkopf-3 Promotes the Development of Renal Atrophy and Fibrosis. JCI Insight, 1, e84916. [Google Scholar] [CrossRef] [PubMed]
[19] Schunk, S.J., Speer, T., Petrakis, I., et al. (2021) Dickkopf 3-a Novel Biomarker of the “Kidney Injury Continuum”. Nephrology Dialysis Transplantation, 36, 761-767. [Google Scholar] [CrossRef] [PubMed]
[20] 廖永丽, 李均. 基于Hedgehog信号通路的中药抗肾纤维化研究进展[J]. 医学综述, 2021, 27(16): 3137-3142.
[21] Li, L.Y., Zhou, G., Fu, R., et al. (2021) Polysaccharides Extracted from Balanophora Polyandra Griff (BPP) Ameliorate Renal Fibrosis and EMT via Inhibiting the Hedgehog Pathway. Journal of Cellular and Molecular Medicine, 25, 2828-2840. [Google Scholar] [CrossRef] [PubMed]
[22] Effendi, W. and Nagano, T. (2021) The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time. International Journal of Molecular Sciences, 23, Article No. 171. [Google Scholar] [CrossRef] [PubMed]
[23] 李庆. Hedgehog信号通路在肾纤维化中的研究进展[J]. 医学研究生学报, 2019, 32(10): 1089-1093.
[24] Kramann, R., Fleig, S.V., et al. (2015) Pharmacological GLI2 Inhibition Prevents Myofibroblast Cell-Cycle Progression and Reduces Kidney Fibrosis. Journal of Clinical Investigation, 125, 2935-2951. [Google Scholar] [CrossRef
[25] Smelkinson, M.G. (2017) The Hedgehog Signaling Pathway Emerges as a Pathogenic Target. Journal of Developmental Biology, 5, Article No. 14. [Google Scholar] [CrossRef] [PubMed]
[26] Zhou, D., Tan, R.J. and Liu Y. (2016) Sonic Hedgehog Signaling in Kidney Fibrosis: A Master Communicator. Science China Life Sciences, 59, 920-929. [Google Scholar] [CrossRef] [PubMed]
[27] Schunk, S.J., Floege, J., Fliser, D., et al. (2021) WNT-β-Catenin Signalling—A Versatile Player in Kidney Injury and Repair. Nature Reviews. Nephrology, 17, 172-184. [Google Scholar] [CrossRef] [PubMed]
[28] Longhitano, L., Tibullo, D., Vicario, N., et al. (2021) IGFBP-6/Sonic Hedgehog/TLR4 Signalling Axis Drives Bone Marrow Fibrotic Transformation in Primary Myelofibrosis. Aging, 13, 25055-25071. [Google Scholar] [CrossRef] [PubMed]
[29] Wang, S., et al. (2021) Insulin-Like Growth Factor Binding Proteins in Kidney Disease. Frontiers in Pharmacology, 29, 89-103. [Google Scholar] [CrossRef] [PubMed]
[30] Wang, S.Q., et al. (2018) The Impact of the Glomerular Filtration Rate on the Human Plasma Proteome. Proteomics—Clinical Applications, 12, Article ID: 1700067. [Google Scholar] [CrossRef] [PubMed]
[31] Liso, A., Santina, V., Daniela, C.A.R., et al. (2022) IGFBP-6: At the Crossroads of Immunity, Tissue Repair and Fibrosis. International Journal of Molecular Sciences, 23, Article No. 4358. [Google Scholar] [CrossRef] [PubMed]
[32] 王长江, 王岚, 邹新蓉, 等. Klotho基因调节生长激素分泌机制的研究进展[J]. 中国中西医结合肾病杂志, 2022, 23(7): 643-645.
[33] Neyra, J.A., Ming, C.H. and Moe, O.W. (2020) Klotho in Clinical Nephrology: Diagnostic and Therapeutic Implications. Clinical Journal of the American Society of Nephrology, 16, 162-176. [Google Scholar] [CrossRef
[34] 陈静, 章晓燕, 丁小强. Klotho蛋白在慢性肾脏病中作用的研究进展[J]. 中国临床医学, 2018, 25(1): 129-131.
[35] 刘其锋, 缪静龙. Klotho抑制肾间质纤维化的作用及机制[J]. 医学综述, 2019, 25(20): 3985-3986.
[36] Wu, W.J., et al. (2022) Smad3 Signatures in Renal Inflammation and Fibrosis. International Journal of Biological Sciences, 18, 2795-2806. [Google Scholar] [CrossRef] [PubMed]
[37] 丁华琳, 李扬扬, 于丰源, 等. 达格列净通过Klotho/TGF-β1通路抑制糖尿病肾病大鼠肾纤维化的作用[J]. 山东大学学报(医学版), 2020, 58(3): 75-80.
[38] 曼刘, 春刘, 刚刘. IgA肾病患者肾组织Klotho蛋白与肾纤维化的关系[J]. 吉林医学, 2019, 12(4): 2701-2704.
[39] 陈燕玲, 罗婷, 高昕乐, 等. 碘普罗胺对HK-2细胞凋亡及对Klotho/Wnt/β-Catenin信号通路的影响[J]. 实用医学杂志, 2019, 35(5): 729-733.
[40] Wang, Q., Ren, D.J., Li, Y.B., et al. (2019) Klotho Attenuates Diabetic Nephropathy in db/db Mice and Ameliorates High Glucose-Induced Injury of Human Renal Glomerular Endothelial Cells. Cell Cycle, 18, 696-707. [Google Scholar] [CrossRef] [PubMed]
[41] 拜霖楠, 程虹, 杨敏, 等. α-klotho蛋白拮抗瘦素损伤小鼠足细胞的实验研究[J]. 中国中西医结合肾病杂志, 2016, 17(7): 573-577.
[42] Vogt, I., Dieter, H. and Leifheit-Nestler, M. (2019) FGF23 and Phosphate-Cardiovascular Toxins in CKD. Toxins (Basel), 11, Article No. 647. [Google Scholar] [CrossRef] [PubMed]
[43] Mace, M.L., Klaus, O. and Lewin, E. (2020) New Aspects of the Kidney in the Regulation of Fibroblast Growth Factor 23 (FGF23) and Mineral Homeostasis. International Journal of Molecular Sciences, 21, Article No. 8810. [Google Scholar] [CrossRef] [PubMed]
[44] Kawai, M. (2016) The FGF23/Klotho Axis in the Regulation of Mineral and Metabolic Homeostasis. Hormone Molecular Biology and Clinical Investigation, 28, 55-67. [Google Scholar] [CrossRef] [PubMed]
[45] Komaba, H. and Lanske, B. (2018) Role of Klotho in Bone and Implica-tion for CKD. Current Opinion in Nephrology and Hypertension, 27, 298-304. [Google Scholar] [CrossRef
[46] Scholze, A., Liu, Y., Pedersen, L., et al. (2014) Soluble α-Klotho and Its Relation to Kidney Function and Fibroblast Growth Factor-23. The Journal of Clinical Endocrinology & Metabolism, 99, E855-E861. [Google Scholar] [CrossRef] [PubMed]
[47] Saha, S., Brigitta, B., Emiliano, P., et al. (2020) An Overview of Nrf2 Sig-naling Pathway and Its Role in Inflammation. Molecules (Basel, Switzerland), 25, Article No. 5474. [Google Scholar] [CrossRef] [PubMed]
[48] Hernandez, L.F., Eguchi, N., Whaley, D., et al. (2022) Anti-Oxidative Therapy in Diabetic Nephropathy. Frontiers in Bioscience (Scholar Edition), 14, Article No. 14. [Google Scholar] [CrossRef] [PubMed]
[49] Yao, H.K., Zhang, W.T., Yang, F., et al. (2022) Discovery of Caffeoylisocitric Acid as a Keap1-Dependent Nrf2 Activator and Its Effects in Mesangial Cells under High Glucose. Journal of Enzyme Inhibition and Medicinal Chemistry, 37, 178-188. [Google Scholar] [CrossRef] [PubMed]
[50] Xing, L.N., Guo, H.J., Meng, S.X., et al. (2021) Klotho Ameliorates Diabetic Nephropathy by Activating Nrf2 Signaling Pathway in Podocytes. Biochemical and Biophysical Research Communications, 534, 450-456. [Google Scholar] [CrossRef] [PubMed]
[51] Lim, S.W., Jin, L., Luo, K., et al. (2017) Klotho Enhances FoxO3-Mediated Manganese Superoxide Dismutase Expression by Negatively Regulating PI3K/AKT Pathway during Tacrolimus-Induced Oxidative Stress. Cell Death & Disease, 8, e2972. [Google Scholar] [CrossRef] [PubMed]
[52] Zeldich, E., Chen, C.-D., Colvin, T.A., et al. (2014) The Neuroprotective Effect of Klotho Is Mediated via Regulation of Members of the Redox System. The Journal of Biological Chemistry, 289, 24700-24715. [Google Scholar] [CrossRef
[53] Jiang, W., Xiao, T.L., Han, W.H., et al. (2019) Klotho Inhibits PKCα/p66SHC-Mediated Podocyte Injury in Diabetic Nephropathy. Molecular and Cellular Endocrinology, 494, Article ID: 110490. [Google Scholar] [CrossRef] [PubMed]