Mechanisms of renal tubular injury acceleration by proteinuria

doi:10.3877/cma.j.issn.2095-3216.2014.02.008

Abstract

Abstract:

Proteinuria of different degrees is the most common clinical manifestation in the progression of chronic kidney disease (CKD). More and more studies showed that persistent proteinuria is closely related to renal tubular injury, as urine protein components can play an important pathophysiological role in the activation of renal tubular structural damage and dysfunction, the mechanism of which includes activation of receptor endocytosis pathway, complement activation, activation of the renin-angiotensin system(RAS), up-regulation of chemokines, and induction of apoptosis, etc. This paper has elaborated on the mechanism of renal tubular injury accelerated by proteinuria, providing important ideas and key targets for prevention and treatment of clinical proteinuria-associated renal injuries.

Key words: Proteinuria, Renal tubule, Activation, Injury

Jun Liu, Xiangmei Chen. Mechanisms of renal tubular injury acceleration by proteinuria[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2014, 03(02): 99-103.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhsbyjdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-3216.2014.02.008

https://zhsbyjdzzz.cma-cmc.com.cn/EN/Y2014/V03/I02/99

References 46

1	Regeniter A, Freidank H, Dickenmann M, et al. Evaluation of proteinuria and GFR to diagnose and classify kidney disease:systematic review and proof of concept [J]. Eur J Intern Med,2009,20(6):556-561.
2	Comper WD, Hilliard LM, Nikolic-Paterson DJ, et al. Diseasedependent mechanisms of albuminuria [J]. Am J Physiol Renal Physiol,2008,295(6): F1589-F1600.
3	Baines RJ, Brunskill NJ. The molecular interactions between filtered proteins and proximal tubular cells in proteinuria [J]. Nephron Exp Nephrol,2008,110(2): e67-e71.
4	Lee D, Gleich K, Fraser SA, et al. Limited capacity of proximal tubular proteolysis in mice with proteinuria. Am J Physiol Renal Physiol,2013,304(7): F1009-F1019.
5	Theilig F, Kriz W, Jerichow T, et al. Abrogation of protein uptake through megalin-deficient proximal tubules does not safeguard against tubulointerstitial injury [J]. J Am Soc Nephrol, 2007, 18(6):1824-1834.
6	Amsellem S, Gburek J, Hamard G, et al. Cubilin is essential for albumin reabsorption in the renal proximal tubule [J]. J Am Soc Nephrol,2010,21(11):1859-1867.
7	Weyer K, Storm T, Shan J, et al. Mouse model of proximal tubule endocytic dysfunction [J]. Nephrol Dial Transplant, 2011, 26(11):3446-3451.
8	Grösbeck R. Imerslund-Grösbeck syndrome (selective vitamin B₁₂ malabsorption with proteinuria) [J]. Orphanet J Rare Dis, 2006,1:17.
9	Storm T, Emma F, Verroust PJ, et al. A patient with cubilin deficiency [J]. N Engl J Med,2011,364(1):89-91.
10	Yang J, He Y. Expression of renal cubilin and its potential role in tubulointerstitial inflammation induced by albumin overload [J].Front Med China,2008,2(1):25-34.
11	Liu J, Li K, He Y, et al. Anticubilin antisense RNA ameliorates adriamycin- induced tubulointerstitial injury in experimental rats[J]. Am J Med Sci,2011,342(6):494-502.
12	Zou Z, Chung B, Nguyen T, et al. Linking receptor-mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule [J]. J Biol Chem,2004,279(33):34302-34310.
13	Shah M, Baterina OY Jr, Taupin V, et al. ARH directs megalin to the endocytic recycling compartment to regulate its proteolysis and gene expression [J]. J Cell Biol,2013,202(1):113-127.
14	Diwakar R, Pearson AL, Colville-Nash P, et al. The role played by endocytosis in albumin-induced secretion of TGF-beta1 by proximal tubular epithelial cells[J]. Am J Physiol Renal Physiol,2007,292(5): F1464-F1470.
15	Morita Y, Ikeguchi H, Nakamura J, et al. Complement activation products in the urine from proteinuric patients [J]. J Am Soc Nephrol,2000,11(4):700-707.
16	Gou SJ, Yuan J, Wang C, et al. Alternative complement pathway activation products in urine and kidneys of patients with ANCAassociated GN [J]. Clin J Am Soc Nephrol, 2013, 8 (11):1884-1891.
17	Nangaku M, Pippin J, Couser WG. C6 mediates chronic progression of tubulointerstitial damage in rats with remnant kidneys [J]. J Am Soc Nephrol,2002,13(4):928-936.
18	Abe K, Li K, Sacks SH, et al. The membrane attack complex,C5b-9, up regulates collagen gene expression in renal tubular epithelial cells [J]. Clin Exp Immunol,2004,136(1):60-66.
19	Chen Y, Zhang J, Guo G, et al. Induced B7-H1 expression on human renal tubular epithelial cells by the sublytic terminal complement complex C5b-9 [J]. Mol Immunol, 2009, 46(3):375-383.
20	Sheerin NS, Risley P, Abe K, et al. Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury [J]. FASEB J,2008,22(4):1065-1072.
21	Tang Z, Lu B, Hatch E, et al. C3a mediates epithelial-tomesenchymal transition in proteinuric nephropathy [J]. J Am Soc Nephrol,2009,20(3):593-603.
22	Peake PW, O'Grady S, Pussell BA, et al. C3a is made by proximal tubular HK-2 cells and activates them via the C3a receptor [J].Kidney Int,1999,56(5):1729-1736.
23	Zoja C, Donadelli R, Colleoni S, et al. Protein overload stimulates RANTES production by proximal tubular cells depending on NFkappa B activation [J]. Kidney Int,1998,53(6):1608-1615.
24	Tang S, Leung JCK, Abe K, et al. Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo[J]. J Clin Invest,2003,111(4):515-527.
25	Dizin E, Hasler U, Nlandu-Khodo S, et al. Albuminuria induces a proinflammatory and profibrotic response in cortical collecting ducts via the 24p3 receptor [J]. Am J Physiol Renal Physiol,2013,305(7): F1053-F1063.
26	Morigi M, Macconi D, Zoja C, et al. Protein overload-induced NFkappa B activation in proximal tubular cells requires H₂O₂ through a PKC-dependent pathway [J]. J Am Soc Nephrol, 2002, 13(5):1179-1189.
27	Rangan GK, Wang Y, Tay YC, et al. Inhibition of nuclear factorkappa B activation reduces cortical tubulointerstitial injury in proteinuric rats [J]. Kidney Int,1999,56(1):118-134.
28	Takase O, Hirahashi J, Takayanagi A, et al. Gene transfer of truncated IκBα prevents tubulointerstitial injury [J]. Kidney Int,2003,63(2):501-513.
29	Ghosh SS, Massey HD, Krieg R, et al. Curcumin ameliorates renal failure in 5/6 nephrectomized rats: role of inflammation [J]. Am J Physiol Renal Physiol,2009,296(5): F1146-F1157.
30	Thomas ME, Brunskill NJ, Harris KP, et al. Proteinuria induces tubular cell turnover:a potential mechanism for tubular atrophy[J].Kidney Int,1999,55(3):890-898.
31	Erkan E, De Leon M, Devarajan P. Albumin overload induces apoptosis in LLC-PK1 cells [J]. Am J Physiol Renal Physiol,2001,280(6): F1107-F1114.
32	Morais C, Westhuyzen J, Metharom P, et al. High molecular weight plasma proteins induce apoptosis and Fas/FasL expression in human proximal tubular cells[J]. Nephrol Dial Transplant,2005,20(1):50-58.
33	Erkan E, Devarajan P, Schwartz GJ. Mitochondria are the major targets in albumin-induced apoptosis in proximal tubule cells [J]. J Am Soc Nephrol,2007,18(4):1199-1208.
34	Li X, Pabla N, Wei Q, et al. PKC-delta promotes renal tubular cell apoptosis associated with proteinuria [J]. J Am Soc Nephrol,2010,21(7):1115-1124.
35	Ohse T, Inagi R, Tanaka T, et al. Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal tubular cells [J].Kidney Int,2006,70(8):1447-1455.
36	Wu X, He Y, Jing Y, et al. Albumin overload induces apoptosis in renal tubular epithelial cells through a CHOP-dependent pathway[J]. OMICS,2010,14(1):61-73.
37	Lee EK, Jeong JU, Chang JW, et al. Activation of AMP-activated protein kinase inhibits albumin-induced endoplasmic reticulum stress and apoptosis through inhibition of reactive oxygen species [J].Nephron Exp Nephrol,2012,121(1-2): e38-e48.
38	Shimizu H, Maruyama S, Yuzawa Y, et al. Anti-monocyte chemoattractant protein-1 gene therapy attenuates renal injury induced by protein-overload proteinuria [J]. J Am Soc Nephrol,2003,14(6):1496-1505.
39	Viedt C, Dechend R, Fei J, et al. MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-κB and activating protein 21[J]. J Am Soc Nephrol,2002,13(6):1534-1547.
40	Lai KN, Leung JC, Chan LY, et al. Interaction between proximal tubular epithelial cells and infiltrating monocytes/T cells in the proteinuric state [J]. Kidney Int,2007,71(6):526-538.
41	Yazdani S, Poosti F, Kramer AB, et al. Proteinuria triggers renal lymphangiogenesis prior to the development of interstitial fibrosis[J]. PLoS One,2012,7(11): e50209.
42	Matsui T, Yamagishi S, Ueda S, et al. Irbesartan inhibits albuminelicited proximal tubular cell apoptosis and injury in vitro [J].Protein Pept Lett,2010,17(1):74-77.
43	Takao T, Horino T, Kagawa T, et al. Effects of angiotensin Ⅱtype 1 receptor blocker on albumin-induced cell damage in human renal proximal tubular epithelial cells[J]. Am J Nephrol,2009,29(2):102-108.
44	Wolf G, Schroeder R, Ziyadeh FN, et al. Albumin up-regulates the type Ⅱtransforming growth factor-beta receptor in cultured proximal tubular cells [J]. Kidney Int,2004,66(5):1849-1858.
45	Takase O, Marumo T, Imai N, et al. NF-kappaB-dependent increase in intrarenal angiotensin Ⅱinduced by proteinuria [J].Kidney Int,2005,68(2):464-473.
46	Cao W, Zhou QG, Nie J, et al. Albumin overload activates intrarenal renin-angiotensin system through protein kinase C and NADPH oxidase- dependent pathway [J]. J Hypertens, 2011, 29(7):1411-1421.

[1]	Kai Zhang, Yongjie Qiao, Zhiqiang Lin, Jian Liu, Zequn Deng, Fei Tan, Jiankang Zeng, Jiahuan Li, Peijie Li, Shenghu Zhou. Advances in mechanism of macrophage polarization in periprosthetic osteolysis [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2024, 18(05): 618-625.
[2]	Jie Wu, Zhiqiang Zhou, Jing Fu, Xigong Li, Qin Zhang. Effects of inhaled hydrogen on autophagy and neurological function after spinal cord injury in rats [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(05): 363-371.
[3]	Ziwei Lei, Ping Ling, Zong Shen, Chenru Wei, Banghui Zhu, Guosheng Wu, Yu Sun. Research progress on the construction and application of disease models of lung injury with organoidbased approach [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2024, 19(06): 531-535.
[4]	Xinyuan Yang, Shujun Wang, Cheng He, Xihe Song, Liyun Liu. Research progress on the prevention and treatment of peripherally inserted central venous catheters occlusion in critically burned patients [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2024, 19(05): 443-446.
[5]	Nan Li, Siqi Qiu, Mingyu Xue, Ying Zhang. Self-injurious oral lesions and related diseases management [J]. Chinese Journal of Stomatological Research(Electronic Edition), 2024, 18(05): 307-311.
[6]	Xiliu Zhang, Dongsheng Yu. Causes and prevention strategies of iatrogenic dental trauma [J]. Chinese Journal of Stomatological Research(Electronic Edition), 2024, 18(05): 287-294.
[7]	Mengmeng Han, Xueyuan Feng, Ning Ma. A case of radial nerve injury after modified radical surgery for breast cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2025, 19(01): 117-118.
[8]	Lingkai Meng, Dayong Li, Ning Wang, Guiming Wang, Bingnan Zhang, Ruotong Li, Lifeng Pan. Effect and mechanism of sleeve gastrectomy on obese rats with type 2 diabetes mellitus [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(06): 638-642.
[9]	Xuehu Wang, Yu Zhao. The prevention and treatment of vascular injury complications in complicated abdominal wall hernia surgery [J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2024, 18(06): 616-619.
[10]	Zhengyang Zhou, Kai Chen, Duoliang Qiu, Lening Shao, Haorong Wu, Fengyun Zhong. Analysis and management of postoperative hemorrhage following laparoscopic inguinal hernia repair [J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2024, 18(06): 660-664.
[11]	Lu Sun, Yaling Jiang, Lingjun Chen. Effect of butorphanol on neuroinflammation and JAK2/STAT3 signaling pathway in rats with cerebral ischemia-reperfusion injury [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(06): 344-350.
[12]	Tong Yu, Jianhang Jiao, Weibo Jiang, Zhonghan Wang, Yang Wang, Xuhui Wu, MinFei Wu. Comparative study of postural reduction and internal fixation versus laminectomy reduction and inter-nal fixation in the treatment ofthoracolumbar burst fractures [J]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2024, 10(06): 331-339.
[13]	Ruhai Wang, Shen Wang, Min Zhang, Chun Li, Chao Han, Qiang Yu, Haicheng Hu, Xizhen Li. Analysis of influencing factors of short-term mortality risk in patients with severe traumatic brain injury after decompressive craniectomy [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(05): 285-291.
[14]	Yan Shen, Junfeng Zhang, Chunfang Tang. Predictive value of prognostic nutritional index combined with PCT，CysC，and RBP levels for acute pancreatitis complicated with acute kidney injury [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2024, 14(06): 536-540.
[15]	Shirui Yan, Hui Xiong. Identification of risk factors for acute kidney injury in patients with infective endocarditis and prediction of death risk in such patients with acute kidney injury [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(07): 618-624.

Please choose a citation manager

Content to export