骨桥蛋白与肾结石形成机制的研究进展
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摘要
骨桥蛋白(OPN)为泌尿系结石基质主要有机成分之一,在肾结石患者及动物模型肾组织内含量明显增高。在肾结石形成各阶段包括晶体黏附、氧化应激、细胞凋亡等过程中扮演关键角色。OPN大量表达将导致晶体沉积,结石形成,最终造成肾脏细胞损伤。抗OPN抗体、抗氧化物及凋亡通路抑制剂能显著减轻OPN介导的结石形成。本综述旨在讨论近年来骨桥蛋白在肾结石形成机制中的新进展以及针对OPN的新的结石预防治疗靶点。
OPN is one of the main components of the organic phase of stone, which is highly expressed in the renal tissue of the kidney stones patients and animal stone models, and plays an important role in the process of crystal aggregation and adhesion, oxidative stress of renal tubular epithelial cells and apoptosis. A large amount of OPN expression will lead to crystal deposition, stone formation, resulting in kidney cell damage. OPN antibodies, antioxidants and apoptotic pathway inhibitors can significantly reduce OPN mediated stone formation. This review aims to discuss recent advances of the role of osteopontin in the formation of kidney stones and the new stone prevention and treatment target for OPN.
OPN is one of the main components of the organic phase of stone, which is highly expressed in the renal tissue of the kidney stones patients and animal stone models, and plays an important role in the process of crystal aggregation and adhesion, oxidative stress of renal tubular epithelial cells and apoptosis. A large amount of OPN expression will lead to crystal deposition, stone formation, resulting in kidney cell damage. OPN antibodies, antioxidants and apoptotic pathway inhibitors can significantly reduce OPN mediated stone formation. This review aims to discuss recent advances of the role of osteopontin in the formation of kidney stones and the new stone prevention and treatment target for OPN.
引文
[1]Romero V,Akpinar H,Assimos DG.Kidney stones:a global picture of prevalence,incidence,and associated risk factors[J].Rev Urol,2010,12(2-3):86-96.
[2]米华,邓耀良.中国尿石症的流行病学特征[J].中华泌尿外科杂志,2003,24(10):715-716.
[3]Rodgers AL.Physicochemical mechanisms of stone formation[J].Urolithiasis,2017,45(1):27-32.
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[5]Yasui T,Okada A,Hamamoto S,et al.Pathophysiologybased treatment of urolithiasis[J].Int J Urol,2017,24(1):32-38.
[6]Chen Q,Shou P,Zhang L,et al.An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells[J].Stem Cells,2014,32(2):327-337.
[7]Caballero D,Li Y,Ponsetto J,et al.Impaired urinary osteopontin excretion in Npt2a-/-mice[J].Am J Physiol Renal Physiol,2017,312(1):F77-F83.
[8]Hamamoto S,Yasui T,Okada A,et al.Crucial role of the cryptic epitope SLAYGLR within osteopontin in renal crystal formation of mice[J].J Bone Miner Res,2011,26(12):2967-2977.
[9]Lee SY,Lee SJ,Piao HL,et al.Hydration status affects osteopontin expression in the rat kidney[J].J Vet Sci,2016,17(3):269-277.
[10]Inoue M,Shinohara ML.Intracellular osteopontin(i OPN)and immunity[J].Immunol Res,2011,49(1-3):160-172.
[11]Kohri K,Yasui T,Okada A,et al.Biomolecular mechanism of urinary stone formation involving osteopontin[J].Urol Res,2012,40(6):623-637.
[12]Taguchi K,Hamamoto S,Okada A,et al.Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers[J].J Am Soc Nephrol,2017,28(1):333-347.
[13]Kolbach-Mandel AM,Mandel NS,Hoffmann BR,et al.Stone former urine proteome demonstrates a cationic shift in protein distribution compared to normal[J].Urolithiasis,2017,45(4):337-346.
[14]Liu Y,Xu H,Zhong W,et al.Organic Selenium Alleviated the Formation of Ethylene Glycol-Induced Calcium Oxalate Renal Calculi by Improving Osteopontin Expression and Antioxidant Capability in Dogs[J].Biol Trace Elem Res,2015,168(2):392-400.
[15]Tsuji H,Shimizu N,Nozawa M,et al.Osteopontin knockdown in the kidneys of hyperoxaluric rats leads to reduction in renal calcium oxalate crystal deposition[J].Urolithiasis,2014,42(3):195-202.
[16]Gan QZ,Sun XY,Ouyang JM.Adhesion and internalization differences of COM nanocrystals on Vero cells before and after cell damage[J].Mater Sci Eng C Mater Biol Appl,2016,59:286-295.
[17]Mo L,Liaw L,Evan AP,et al.Renal calcinosis and stone formation in mice lacking osteopontin,Tamm-Horsfall protein,or both[J].Am J Physiol Renal Physiol,2007,293(6):1935-1943.
[18]Nene SS,Hunter GK,Goldberg HA,et al.Reversible inhibition of calcium oxalate monohydrate growth by an osteopontin phosphopeptide[J].Langmuir,2013,29(21):6287-6295.
[19]Ouyang JM,Yao XQ,Tan J,et al.Renal epithelial cell injury and its promoting role in formation of calcium oxalate monohydrate[J].J Biol Inorg Chem,2011,16(3):405-416.
[20]Kumar V,Pe觡a de la Vega L,Farell G,et al.Urinary macromolecular inhibition of crystal adhesion to renal epithelial cells is impaired in male stone formers[J].Kidney Int,2005,68(4):1784-1792.
[21]Hirose M,Tozawa K,Okada A,et al.Role of osteopontin in early phase of renal crystal formation:immunohistochemical and microstructural comparisons with osteopontin knock-out mice[J].Urol Res,2012,40(2):121-129.
[22]Okada A,Nomura S,Saeki Y,et al.Morphological conversion of calcium oxalate crystals into stones is regulated by osteopontin in mouse kidney[J].J Bone Miner Res,2008,23(10):1629-1637.
[23]Khan SR.Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation:evidence from clinical and experimental investigations[J].J Urol,2013,189(3):803-811.
[24]Sener TE,Sener G,Cevik O,et al.The Effects of Melatonin on Ethylene Glycol-induced Nephrolithiasis:Role on Osteopontin m RNA Gene Expression[J].Urology,2017,99:287.e9-287.e15.
[25]Hirose M,Yasui T,Okada A,et al.Renal tubular epithelial cell injury and oxidative stress induce calcium oxalate crystal formation in mouse kidney[J].Int J Urol,2010,17(1):83-92.
[26]Zuo J,Khan A,Glenton PA,et al.Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy-L-proline-induced hyperoxaluria in the male Sprague-Dawley rats[J].Nephrol Dial Transplant,2011,26(6):1785-1796.
[27]Niimi K,Yasui T,Hirose M,et al.Mitochondrial permeability transition pore opening induces the initial process of renal calcium crystallization[J].Free Radic Biol Med,2012,52(7):1207-1217.
[28]Niimi K,Yasui T,Okada A,et al.Novel effect of the inhibitor of mitochondrial cyclophilin?D activation,Nmethyl-4-isoleucine cyclosporin,on renal calcium crystallization[J].Int J Urol,2014,21(7):707-713.
[29]Bhardwaj R,Bhardwaj A,Tandon C,et al.Implication of hyperoxaluria on osteopontin and ER stress mediated apoptosis in renal tissue of rats[J].Exp Mol Pathol,2017,102(3):384-390.
[30]Dalal S,Zha Q,Daniels CR,et al.Osteopontin stimulates apoptosis in adult cardiac myocytes via the involvement of CD44 receptors,mitochondrial death pathway,and endoplasmic reticulum stress[J].Am J Physiol Heart Circ Physiol,2014,306(8):H1182-H1191.
[2]米华,邓耀良.中国尿石症的流行病学特征[J].中华泌尿外科杂志,2003,24(10):715-716.
[3]Rodgers AL.Physicochemical mechanisms of stone formation[J].Urolithiasis,2017,45(1):27-32.
[4]Canales BK,Anderson L,Higgins L,et al.Proteome of human calcium kidney stones[J].Urology,2010,76(4):1017.e13-e20.
[5]Yasui T,Okada A,Hamamoto S,et al.Pathophysiologybased treatment of urolithiasis[J].Int J Urol,2017,24(1):32-38.
[6]Chen Q,Shou P,Zhang L,et al.An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells[J].Stem Cells,2014,32(2):327-337.
[7]Caballero D,Li Y,Ponsetto J,et al.Impaired urinary osteopontin excretion in Npt2a-/-mice[J].Am J Physiol Renal Physiol,2017,312(1):F77-F83.
[8]Hamamoto S,Yasui T,Okada A,et al.Crucial role of the cryptic epitope SLAYGLR within osteopontin in renal crystal formation of mice[J].J Bone Miner Res,2011,26(12):2967-2977.
[9]Lee SY,Lee SJ,Piao HL,et al.Hydration status affects osteopontin expression in the rat kidney[J].J Vet Sci,2016,17(3):269-277.
[10]Inoue M,Shinohara ML.Intracellular osteopontin(i OPN)and immunity[J].Immunol Res,2011,49(1-3):160-172.
[11]Kohri K,Yasui T,Okada A,et al.Biomolecular mechanism of urinary stone formation involving osteopontin[J].Urol Res,2012,40(6):623-637.
[12]Taguchi K,Hamamoto S,Okada A,et al.Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers[J].J Am Soc Nephrol,2017,28(1):333-347.
[13]Kolbach-Mandel AM,Mandel NS,Hoffmann BR,et al.Stone former urine proteome demonstrates a cationic shift in protein distribution compared to normal[J].Urolithiasis,2017,45(4):337-346.
[14]Liu Y,Xu H,Zhong W,et al.Organic Selenium Alleviated the Formation of Ethylene Glycol-Induced Calcium Oxalate Renal Calculi by Improving Osteopontin Expression and Antioxidant Capability in Dogs[J].Biol Trace Elem Res,2015,168(2):392-400.
[15]Tsuji H,Shimizu N,Nozawa M,et al.Osteopontin knockdown in the kidneys of hyperoxaluric rats leads to reduction in renal calcium oxalate crystal deposition[J].Urolithiasis,2014,42(3):195-202.
[16]Gan QZ,Sun XY,Ouyang JM.Adhesion and internalization differences of COM nanocrystals on Vero cells before and after cell damage[J].Mater Sci Eng C Mater Biol Appl,2016,59:286-295.
[17]Mo L,Liaw L,Evan AP,et al.Renal calcinosis and stone formation in mice lacking osteopontin,Tamm-Horsfall protein,or both[J].Am J Physiol Renal Physiol,2007,293(6):1935-1943.
[18]Nene SS,Hunter GK,Goldberg HA,et al.Reversible inhibition of calcium oxalate monohydrate growth by an osteopontin phosphopeptide[J].Langmuir,2013,29(21):6287-6295.
[19]Ouyang JM,Yao XQ,Tan J,et al.Renal epithelial cell injury and its promoting role in formation of calcium oxalate monohydrate[J].J Biol Inorg Chem,2011,16(3):405-416.
[20]Kumar V,Pe觡a de la Vega L,Farell G,et al.Urinary macromolecular inhibition of crystal adhesion to renal epithelial cells is impaired in male stone formers[J].Kidney Int,2005,68(4):1784-1792.
[21]Hirose M,Tozawa K,Okada A,et al.Role of osteopontin in early phase of renal crystal formation:immunohistochemical and microstructural comparisons with osteopontin knock-out mice[J].Urol Res,2012,40(2):121-129.
[22]Okada A,Nomura S,Saeki Y,et al.Morphological conversion of calcium oxalate crystals into stones is regulated by osteopontin in mouse kidney[J].J Bone Miner Res,2008,23(10):1629-1637.
[23]Khan SR.Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation:evidence from clinical and experimental investigations[J].J Urol,2013,189(3):803-811.
[24]Sener TE,Sener G,Cevik O,et al.The Effects of Melatonin on Ethylene Glycol-induced Nephrolithiasis:Role on Osteopontin m RNA Gene Expression[J].Urology,2017,99:287.e9-287.e15.
[25]Hirose M,Yasui T,Okada A,et al.Renal tubular epithelial cell injury and oxidative stress induce calcium oxalate crystal formation in mouse kidney[J].Int J Urol,2010,17(1):83-92.
[26]Zuo J,Khan A,Glenton PA,et al.Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy-L-proline-induced hyperoxaluria in the male Sprague-Dawley rats[J].Nephrol Dial Transplant,2011,26(6):1785-1796.
[27]Niimi K,Yasui T,Hirose M,et al.Mitochondrial permeability transition pore opening induces the initial process of renal calcium crystallization[J].Free Radic Biol Med,2012,52(7):1207-1217.
[28]Niimi K,Yasui T,Okada A,et al.Novel effect of the inhibitor of mitochondrial cyclophilin?D activation,Nmethyl-4-isoleucine cyclosporin,on renal calcium crystallization[J].Int J Urol,2014,21(7):707-713.
[29]Bhardwaj R,Bhardwaj A,Tandon C,et al.Implication of hyperoxaluria on osteopontin and ER stress mediated apoptosis in renal tissue of rats[J].Exp Mol Pathol,2017,102(3):384-390.
[30]Dalal S,Zha Q,Daniels CR,et al.Osteopontin stimulates apoptosis in adult cardiac myocytes via the involvement of CD44 receptors,mitochondrial death pathway,and endoplasmic reticulum stress[J].Am J Physiol Heart Circ Physiol,2014,306(8):H1182-H1191.