TRPC6与肾脏疾病关系的研究进展

曹珊; 刘运广

doi:10.7499/j.issn.1008-8830.2018.01.015

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中国当代儿科杂志 ›› 2018, Vol. 20 ›› Issue (1) : 72-76. DOI: 10.7499/j.issn.1008-8830.2018.01.015

综述

TRPC6与肾脏疾病关系的研究进展

曹珊¹, 刘运广²

作者信息 +

Research advances in the association between transient receptor potential cation channel 6 and kidney disease

CAO Shan¹, LIU Yun-Guang²

Author information +

文章历史 +

摘要

瞬时受体电位阳离子通道蛋白6（TRPC6）是由TRPC6基因编码的瞬时受体超家族成员之一，在人体内各组织或器官广泛表达，在肾小球足细胞也有表达。TRPC6与podocin、nephrin、ACTN4及CD2AP等多种裂孔隔膜（SD）蛋白相互作用共同维系肾小球足细胞的结构及功能。多因素作用导致肾小球足细胞损伤引起SD的足突融合是肾脏疾病最主要的形态学改变。该文就TRPC6生物学功能及其对肾脏疾病的影响作一简述。

Abstract

Transient receptor potential cation channel 6 (TRPC6) is a member of the transient receptor superfamily encoded by the TRPC6 gene and is widely expressed in tissues and organs of the human body, especially in the glomerular podocytes. TRPC6 interacts with various slit diaphragm (SD) proteins including podocin, nephrin, ACTN4, and CD2AP to maintain the normal structure and function of glomerular podocytes. Foot process fusion caused by podocyte damage due to various factors is the most important morphological change in kidney disease. This article reviews the biological function of TRPC6 and its effect on kidney disease.

导出引用

曹珊, 刘运广. TRPC6与肾脏疾病关系的研究进展[J]. 中国当代儿科杂志. 2018, 20(1): 72-76 https://doi.org/10.7499/j.issn.1008-8830.2018.01.015

CAO Shan, LIU Yun-Guang. Research advances in the association between transient receptor potential cation channel 6 and kidney disease[J]. Chinese Journal of Contemporary Pediatrics. 2018, 20(1): 72-76 https://doi.org/10.7499/j.issn.1008-8830.2018.01.015

参考文献

[1] Zolotas E, Krishnan RG. Nephrotic syndrome[J]. Paediatr Child Health, 2016, 26(8):349-352.
[2] Müller-Deile J, Schiffer M. Podocyte directed therapy of nephrotic syndrome-can we bring the inside out[J]. Pediatr Nephrol, 2016, 31(3):393-405.
[3] Raij L, Tian R, Wong JS, et al. Podocyte injury:the role of proteinuria, urinary plasminogen, and oxidative stress[J]. Am J Physiol Renal Physiol, 2016, 311(6):F1308-F1317.
[4] 郝胜, 吴滢, 何威逊, 等. 儿童原发性肾病综合征肾组织瞬时受体电位阳离子通道蛋白6表达及意义[J]. 临床儿科杂志, 2017, 35(7):498-502.
[5] Ilatovskaya DV, Staruschenko A. TRPC6 channel as an emerging determinant of the podocyte injury susceptibility in kidney diseases[J]. Am J Physiol Renal Physiol, 2015, 309(5):F393-F397.
[6] Dogra S, Kaskel F. Steroid-resistant nephrotic syndrome:a persistent challenge for pediatric nephrology[J]. Pediatr Nephrol, 2017, 32(6):965-974.
[7] 郭晓红, 张涵, 胡杰, 等. 瞬时受体电位阳离子通道蛋白6和整合素连接激酶在以蛋白尿为主要表现的慢性肾脏病中的表达[J]. 中华肾脏病杂志, 2017, 33(5):378-384.
[8] Ilatovskaya DV, Palygin O, Chubinskiy-Nadezhdin V, et al. Angiotensin Ⅱ has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli[J]. Kidney Int, 2014, 86(3):506-514.
[9] Huang H, You Y, Lin X, et al. Inhibition of TRPC6 signal pathway alleviates podocyte injury induced by TGF-β1[J]. Cell Physiol Biochem, 2017, 41(1):163-172.
[10] Koitabashi N, Aiba T, Hesketh GG, et al. Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation novel mechanism of cardiac stress modulation by PDE5 inhibition[J]. J Mol Cell Cardiol, 2009, 48(4):713-724.
[11] Pollak MR, Quaggin SE, Hoenig MP, et al. The glomerulus:the sphere of influence[J]. Clin J Am Soc Nephrol, 2014, 9(8):1461-1469.
[12] Wieder N, Greka A. Calcium, TRPC channels, and regulation of the actin cytoskeleton in podocytes:towards a future of targeted therapies[J]. Pediatr Nephrol, 2016, 31(7):1047-1054.
[13] Riehle M, Büscher AK, Gohlke BO, et al. TRPC6 G757D loss-of-function mutation associates with FSGS[J]. J Am Soc Nephrol, 2016, 27(9):2771-2783.
[14] Möller CC, Wei C, Altintas MM, et al. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease[J]. J Am Soc Nephrol, 2007, 18(1):29-36.
[15] Winn MP, Conlon PJ, Lynn KL, et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis[J]. Science, 2005, 308(5729):1801-1804
[16] 彭梅,李贵森. TRPC6基因突变致局灶节段性肾小球硬化的研究进展[J]. 实用医院临床杂志, 2016, 13(3):170-173.
[17] Kuang XY, Huang WY, Xu H, et al. 254C>G:a TRPC6 promoter variation associated with enhanced transcription and steroid-resistant nephrotic syndrome in Chinese children[J]. Pediatr Res, 2013, 74:511-516.
[18] Zhang Q, Ma J, Xie J, et al. Screening of ACTN4 and TRPC6 mutations in a Chinese cohort of patients with adult-onset familial focal segmental glomerulosclerosis[J]. Contrib Nephrol, 2013, 181:91-100.
[19] Mahesh Kumar KB, Prabha S, Ramprasad E, et al. TRPC6 gene promoter polymorphisms in steroid resistant nephrotic syndrome children[J]. J Nephropharmacol, 2017, 4(2):52-56
[20] Iqbal Z, Sayer JA. Case Report:Making a diagnosis of familial renal disease -clinical and patient perspectives[J]. F 1000Res, 2017, 6:470.
[21] Reiser J, Polu KR, Möller CC, et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function[J]. Nat Genet, 2005, 37(7):739-744.
[22] Hofstra JM, Coenen MJ, Schijvenaars MM, et al. TRPC6 single nucleotide polymorphisms and progression of idiopathic membranous nephropathy[J]. PLoS One, 2014, 9(7):e102065.
[23] Chen WC, Chen SY, Chen CH. et al. Lack of association between transient receptor potential cation channel 6 polymorphisms and primary membranous glomerulonephritis[J]. Ren Fail, 2010, 32(6):666-672.
[24] Kistler AD, Singh G, Altintas MM, et al. Transient receptor potential channel 6(TRPC6) protects podocytes during complement-mediated glomerular disease[J]. J Biol Chem, 2013, 288(51):36598-36609.
[25] Yu S, Yu L. Dexamethasone resisted podocyte injury via stabilizing TRPC6 expression and distribution[J]. Evid Based Complement Alternat Med, 2012, 2012:652059.
[26] Sun X, Fang Z, Zhu Z, et al. Effect of down-regulation of TRPC6 on the puromycin aminonucleoside-induced apoptosis of mouse podocytes[J]. J Huazhong Univ Sci Technolog(Med Sci), 2009, 29(4):417-422.
[27] Sonneveld R, van der Vlag J, Baltissen MP, et al. Glucose specifically regulates TRPC6 expression in the podocyte in an AngⅡ-dependent manner[J]. Am J Pathol, 2014, 184(6):1715-1726.
[28] 胡春丽, 谢席胜, 冯胜刚. 高糖对小鼠足细胞TRPC6表达的影响[J]. 西部医学, 2017, 29(1):22-26.
[29] 胡春丽, 谢席胜, 冯胜刚. 厄贝沙坦对高糖诱导的小鼠足细胞瞬时受体电位阳离子通道蛋白6表达的影响[J]. 临床肾脏病杂志, 2016, 16(12):744-749.
[30] 任直亲,范慧,李芳芳, 等.缬沙坦对糖尿病肾病大鼠肾脏TRPC6表达的影响[J].糖尿病新世界, 2016, 19(11):48-49.
[31] Yao XM, Liu YJ, Wang YM, et al. Astragaloside IV prevents high glucose-induced podocyte apoptosis via downregulation of TRPC6[J]. Mol Med Report, 2016, 13(6):5149-5156.
[32] Ma R, Liu L, Jiang W, et al. FK506 ameliorates podocyte injury in type 2 diabetic nephropathy by down-regulating TRPC6 and NFAT expression[J]. Int J Clin Exp Pathol, 2016, 8(11):14063-14074.
[33] Ilatovskaya DV, Levchenko V, Lowing A. et al. Podocyte injury in diabetic nephropathy:implications of angiotensin Ⅱ-dependent activation of TRPC channels[J]. Sci Rep, 2015, 5:17637.
[34] do Nascimento JF, Canani LH, Gerchman F, et al. Messenger RNA levels of podocyte-associated proteins in subjects with different degrees of glucose tolerance with or without nephropathy[J]. BMC Nephrol, 2013, 14:214.
[35] Wu YL, Xie J, An SW, et al. Inhibition of TRPC6 channels ameliorates renal fibrosis and contributes to renal protection by soluble klotho[J]. Kidney Int, 2017, 91(4):830-841.
[36] 张磊, 陈秀萍, 蒋玲, 等. 全反式维甲酸对肾小球硬化大鼠肾小球TRPC6表达的影响[J]. 实用医学杂志, 2016, 32(23):3827-3831.
[37] 黄海庭, 吴好好, 覃幼玲, 等. 黄芪总苷对TGF-β1诱导下足细胞TRPC6表达的影响[J]. 中国免疫学杂志, 2017, 33(3):370-373.
[38] Hagmann H, Mangold N, Rinschen MM, et al. Proline-dependent and basophilic kinases phosphorylate human TRPC6 at serine 14 to control channel activity through increased membrane expression[J]. FASEB J, 2017 Sep 6. pii:fj.201700309R.
[39] Urban N, Wang L, Kwiek S, et al. Identification and validation of larixyl acetate as a potent TRPC6 inhibitor[J]. Mol Pharmacol, 2016, 89(1):197-213.
[40] Kim EY, Roshanravan H, Dryer SE, et al. Changes in podocyte TRPC channels evoked by plasma and sera from patients with recurrent FSGS and by putative glomerular permeability factors[J]. Biochim Biophys Acta, 2017, 1863(9):2342-2354.