Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy (original) (raw)
Cooper, M. E. Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy. Diabetologia44, 1957–1972 (2001). ArticleCASPubMed Google Scholar
Wolf, G. New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology. Eur. J. Clin. Invest.34, 785–796 (2004). ArticleCASPubMed Google Scholar
Martini, S., Eichinger, F., Nair, V. & Kretzler, M. Defining human diabetic nephropathy on the molecular level: integration of transcriptomic profiles with biological knowledge. Rev. Endocr. Metab. Disord.9, 267–274 (2008). ArticleCASPubMedPubMed Central Google Scholar
Zandi-Nejad, K., Eddy, A. A., Glassock, R. J. & Brenner, B. M. Why is proteinuria an ominous biomarker of progressive kidney disease? Kidney Int. Suppl.92, S76–S89 (2004). ArticleCAS Google Scholar
Abbate, M., Zoja, C. & Remuzzi, G. How does proteinuria cause progressive renal damage? J. Am. Soc. Nephrol.17, 2974–2984 (2006). ArticleCASPubMed Google Scholar
Vilcek, J. in The Cytokine Handbook 4th edn (eds Thomson, A. W. & Lotze, M. T.) 3–18 (Academic Press, London, 2003). Book Google Scholar
Alexandraki, K. et al. Inflammatory process in type 2 diabetes. The role of cytokines. Ann. NY Acad. Sci.1084, 89–117 (2006). ArticleCASPubMed Google Scholar
Hasegawa, G. et al. Possible role of tumor necrosis factor and interleukin-1 in the development of diabetic nephropathy. Kidney Int.40, 1007–1012 (1991). ArticleCASPubMed Google Scholar
Hasegawa, G., Nakano, K. & Kondo, M. Role of TNF and IL-1 in the development of diabetic nephropathy. Nefrologia15, 1–4 (1995). Google Scholar
Nakamura, T. et al. mRNA expression of growth factors in glomeruli from diabetic rats. Diabetes42, 450–456 (1993). ArticleCASPubMed Google Scholar
Sugimoto, H., Shikata, K., Wada, J., Horiuchi, S. & Makino, H. Advanced glycation end products-cytokine-nitric oxide sequence pathway in the development of diabetic nephropathy: aminoguanidine ameliorates the overexpression of tumour necrosis factor-α and inducible oxide synthase in diabetic rat glomeruli. Diabetologia42, 878–886 (1999). ArticleCASPubMed Google Scholar
Navarro, J. F. & Mora, C. Role of inflammation in diabetic complications. Nephrol. Dial. Transplant.20, 2601–2604 (2005). ArticlePubMed Google Scholar
Navarro-González, J. F. & Mora-Fernández, C. The role of inflammatory cytokines in diabetic nephropathy. J. Am. Soc. Nephrol.19, 433–442 (2008). ArticleCASPubMed Google Scholar
Sassy-Prigent, C. et al. Early glomerular macrophage recruitment in streptozotocin-induced diabetic rats. Diabetes49, 466–475 (2000). ArticleCASPubMed Google Scholar
Navarro, J. F. et al. Tumour necrosis factor-α gene expression in diabetic nephropathy: relationship with urinary albumin excretion and effect of angiotensin-converting enzyme inhibition. Kidney Int. Suppl.99, S98–S102 (2005). ArticleCAS Google Scholar
Navarro, J. F., Milena, F. J., Mora, C., León, C. & García, J. Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. Am. J. Nephrol.26, 562–570 (2006). ArticleCASPubMed Google Scholar
Pfeilschifter, J., Pignat, W., Vosbeck, K. & Märki, F. Interleukin 1 and tumor necrosis factor synergistically stimulate prostaglandin synthesis and phospholipase A2 release from rat renal mesangial cells. Biochem. Biophys. Res. Commun.159, 385–394 (1989). ArticleCASPubMed Google Scholar
Pfeilschifter, J. & Mühl, H. Interleukin-1 and tumor necrosis factor potentiate angiotensin II- and calcium ionophore-stimulated prostaglandin E2 synthesis in rat renal mesangial cells. Biochem. Biophys. Res. Commun.169, 585–595 (1990). ArticleCASPubMed Google Scholar
Jones, S., Jones, S. & Phillips, A. O. Regulation of renal proximal tubular epithelial cell hyaluronan generation: implications for diabetic nephropathy. Kidney Int.59, 1739–1749 (2001). ArticleCASPubMed Google Scholar
Royall, J. A. et al. Tumor necrosis factor and interleukin 1 increase vascular endothelial permeability. Am. J. Physiol.257, L339–L410 (1989). Google Scholar
Suzuki, D. et al. In situ hybridization of interleukin 6 in diabetic nephropathy. Diabetes44, 1233–1238 (1995). ArticleCASPubMed Google Scholar
Coleman, D. L. & Ruef, C. Interleukin-6: an autocrine regulator of mesangial cell growth. Kidney Int.41, 604–606 (1992). ArticleCASPubMed Google Scholar
Nosadini, R. et al. Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate. Diabetes49, 476–484 (2000). ArticleCASPubMed Google Scholar
Dalla Vestra, M. et al. Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J. Am. Soc. Nephrol.16 (Suppl. 1), S78–S82 (2005). ArticlePubMed Google Scholar
Sekizuka, K. et al. Detection of serum IL-6 in patients with diabetic nephropathy. Nephron68, 284–285 (1994). ArticleCASPubMed Google Scholar
Thomson, S. C. et al. Ornithine decarboxylase, kidney size, and the tubular hypothesis of glomerular hyperfiltration in experimental diabetes. J. Clin. Invest.107, 217–224 (2001). ArticleCASPubMedPubMed Central Google Scholar
Melnikov, V. Y. et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J. Clin. Invest.107, 1145–1152 (2001). ArticleCASPubMedPubMed Central Google Scholar
Melnikov, V. Y. et al. Neutrophil-independent mechanisms of caspase-1 and IL-18 mediated ischemic acute tubular necrosis in mice. J. Clin. Invest.110, 1083–1091 (2002). ArticleCASPubMedPubMed Central Google Scholar
Miyauchi, K., Takiyama, Y., Honjyo, J., Tatano, M. & Haneda, M. Upregulated IL-18 expression in type 2 diabetic subjects with nephropathy: TGF-β1 enhanced IL-18 expression in human renal proximal tubular epithelial cells. Diabetes Res. Clin. Pract.83, 190–199 (2009). ArticleCASPubMed Google Scholar
Okamura, H. et al. Cloning of a new cytokine that induces IFN-γ production by T cells. Nature378, 88–91 (1995). ArticleCASPubMed Google Scholar
Dai, S. M., Matsuno, H., Nakamura, H., Nishioka, K. & Yudoh, K. Interleukin-18 enhances monocyte tumor necrosis factor α and interleukin-1β production induced by direct contact with T lymphocytes: implications in rheumatoid arthritis. Arthritis Rheum.50, 432–443 (2004). ArticleCASPubMed Google Scholar
Mariño, E. & Cardier, J. E. Differential effects of IL-18 on endothelial cell apoptosis mediated by TNF-α and Fas (CD59). Cytokine22, 142–148 (2003). ArticleCASPubMed Google Scholar
Stuyt, R. J. et al. Selective regulation of intercellular adhesion molecule-1 expression by interleukin-18 and interleukin-12 on human monocytes. Immunology110, 329–334 (2003). ArticleCASPubMedPubMed Central Google Scholar
Moriwaki, Y. et al. Elevated levels of interleukin-18 and tumor necrosis factor-alpha in serum of patients with type 2 diabetes mellitus: relationship with diabetic nephropathy. Metabolism52, 605–608 (2003). ArticleCASPubMed Google Scholar
Mahmoud, R. A., el-Ezz, S. A. & Hegazy, A. S. Increased serum levels of interleukin-18 in patients with diabetic nephropathy. Ital. J. Biochem.53, 73–81 (2004). PubMed Google Scholar
Nakamura, A. et al. Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Care28, 2890–2895 (2005). ArticleCASPubMed Google Scholar
Wong, C. K. et al. Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with nephropathy. Clin. Exp. Immunol.149, 123–131 (2007). ArticleCASPubMedPubMed Central Google Scholar
Araki, S. et al. Predictive impact of elevated serum level of IL-18 for early renal dysfunction in type 2 diabetes: an observational follow-up study. Diabetologia50, 867–873 (2007). ArticleCASPubMed Google Scholar
Fujita, T. et al. Interleukin-18 contributes more closely to the progression of diabetic nephropathy than other diabetic complications. Acta Diabetol. doi:10.1007/s00592-010-0178-4.
Wang, H., Czura, C. J. & Tracey, K. J. in The Cytokine Handbook 4th edn (eds Thomson, A. W. & Lotze, M. T.) 837–860 (Academic Press, London, 2003). Google Scholar
Ortiz, A. et al. Involvement of tumor necrosis factor-alpha in the pathogenesis of experimental and human glomerulonephritis. Adv. Nephrol. Necker Hosp.24, 53–77 (1995). CASPubMed Google Scholar
Laster, S. M., Wood, J. G. & Gooding, L. R. Tumor necrosis factor can induce both apoptotic and necrotic forms of cell lysis. J. Immunol.141, 2629–2634 (1988). CASPubMed Google Scholar
Baud, L., Pérez, J., Friedlander, G. & Ardaillou, R. Tumor necrosis factor stimulates prostaglandin production and cyclic AMP levels in rat cultured mesangial cells. FEBS Lett.239, 50–54 (1998). Article Google Scholar
Wójciak-Stothard, B., Entwistle, A., Garg, R. & Ridley, A. J. Regulation of TNF-α-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells. J. Cell. Physiol.176, 150–165 (1998). ArticlePubMed Google Scholar
Koike, N., Takamura, T. & Kaneko, S. Induction of reactive oxygen species from isolated rat glomerli by protein kinase C activation and TNF-α stimulation, and effects of a phosphodiesterase inhibitor. Life Sci.80, 1721–1728 (2007). ArticleCASPubMed Google Scholar
McCarthy, E. T. et al. TNF-α increases albumin permeability of isolated rat glomeruli through the generation of superoxide. J. Am. Soc. Nephrol.9, 433–438 (1998). CASPubMed Google Scholar
DiPetrillo, K., Coutermarsh, B. & Gesek, F. A. Urinary tumor necrosis factor contributes to sodium retention and renal hypertrophy during diabetes. Am. J. Physiol. Renal Physiol.284, F113–F121 (2003). ArticleCASPubMed Google Scholar
DiPetrillo, K. & Gesek, F. A. Pentoxifylline ameliorates renal tumor necrosis factor expression, sodium retention, and renal hypertrophy in diabetic rats. Am. J. Nephrol.24, 352–359 (2004). ArticleCASPubMed Google Scholar
Schreiner, G. F. & Kohan, D. E. Regulation of renal transport processes and hemodynamics by macrophages and lymphocytes. Am. J. Physiol.258, F761–F767 (1990). CASPubMed Google Scholar
Kalantarinia, K., Awas, A. S. & Siragy, H. M. Urinary and renal interstitial concentrations of TNF-α increase prior to the rise in albuminuria in diabetic rats. Kidney Int.64, 1208–1213 (2003). ArticleCASPubMed Google Scholar
Navarro, J. F., Mora, C., Macía, M. & García, J. Inflammatory parameters are independently associated with urinary albumin excretion in type 2 diabetes mellitus. Am. J. Kidney Dis.42, 53–61 (2003). ArticleCASPubMed Google Scholar
Navarro, J. F., Mora, C., Muros, M. & García, J. Urinary tumor necrosis factor-α excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients. Nephrol. Dial. Transplant.21, 3428–3434 (2006). ArticleCASPubMed Google Scholar
Niewczas, M. A. et al. Serum concentrations of markers of TNFα and Fas-mediated pathways and renal function in nonproteinuric patients with type 1 diabetes. Clin. J. Am. Soc. Nephrol.4, 62–70 (2009). ArticleCASPubMedPubMed Central Google Scholar
Lin, J., Hu, F. B., Mantzoros, C. & Curhan, G. C. Lipid and inflammatory biomarkers and kidney function decline in type 2 diabetes. Diabetologia53, 263–267 (2010). ArticleCASPubMed Google Scholar
Schneider, P. et al. TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-κB. Immunity7, 831–836 (1997). ArticleCASPubMed Google Scholar
Shikata, K. & Makino, H. Role of macrophages in the pathogenesis of diabetic nephropathy. Contrib. Nephrol.134, 46–54 (2001). ArticleCAS Google Scholar
Tesch, G. H. Role of macrophages in complications of type 2 diabetes. Clin. Exp. Pharmacol. Physiol.34, 1016–1019 (2007). ArticleCAS Google Scholar
Chow, F., Ozols, E., Nikolic-Paterson, D. J., Atkins, R. C. & Tesch, G. H. Macrophages in mouse type 2 diabetic nephropathy: correlation with diabetic state and progressive renal injury. Kidney Int.65, 116–128 (2004). ArticleCASPubMed Google Scholar
Bending, J. J., Lobo-Yeo, A., Vergani, D. & Viberti, G. C. Proteinuria and activated T-lymphocytes in diabetic nephropathy. Diabetes37, 507–511 (1988). ArticleCASPubMed Google Scholar
Salozhin, K. V., Nasonov, E. L. & Sura, W. The cellular immunity indices in diabetic nephropathy [Russian]. Ter. Arkh.63, 55–58 (1991). CASPubMed Google Scholar
Fardon, N. J., Wilkinson, R. & Thomas, T. H. Abnormalities in primary granule exocytosis in neutrophils from type I diabetic patients with nephropathy. Clin. Sci. (Lond.)102, 69–75 (2002). ArticleCAS Google Scholar
Takahashi, T. et al. Increased spontaneous adherence of neutrophils from type 2 diabetic patients with overt proteinuria: possible role of the progression of diabetic nephropathy. Diabetes Care23, 417–418 (2000). ArticleCASPubMed Google Scholar
Galkina, E. & Ley, K. Leukocyte recruitment and vascular injury in diabetic nephropathy. J.Am. Soc. Nephrol.17, 368–377 (2006). ArticleCAS Google Scholar
Min, D. et al. Mesangial cell-derived factors alter monocyte activation and function through inflammatory pathways: possible pathogenic role in diabetic nephropathy. Am. J. Physiol. Renal Physiol.297, F1229–F1237 (2009). ArticleCASPubMed Google Scholar
Ruster, C. & Wolf, G. The role of chemokines and chemokine receptors in diabetic nephropathy. Front. Biosci.13, 944–955 (2008). ArticleCASPubMed Google Scholar
Panzer, U., Steinmetz, O. M., Stahl, R. A. & Wolf, G. Kidney diseases and chemokines. Curr. Drug Targets7, 65–80 (2006). ArticleCASPubMed Google Scholar
Chow, Y. et al. Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice. Diabetologia50, 471–480 (2007). ArticleCASPubMed Google Scholar
Chow, Y. et al. Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice. Kidney Int.69, 73–80 (2006). ArticleCASPubMed Google Scholar
Tarabra, E. et al. Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system on nephrin expression in streptozotocin-treated mice and human cultured podocytes. Diabetes54, 2109–2118 (2009). ArticleCAS Google Scholar
Wada, T. et al. Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy. Kidney Int.58, 1492–1498 (2000). ArticleCASPubMed Google Scholar
Tashiro, K. et al. Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), and renal injuries in patients with type 2 diabetic nephropathy. J. Clin. Lab. Anal.16, 1–4 (2002). ArticleCASPubMedPubMed Central Google Scholar
Morii, T. et al. Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy. J. Diabetes Complications17, 11–15 (2003). ArticlePubMed Google Scholar
Lee, E. Y. et al. Monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-β, increases podocyte motility and albumin permeability. Am. J. Physiol. Renal Physiol.297, F85–F94 (2009). ArticleCASPubMedPubMed Central Google Scholar
Janiak, P. et al. Long-term blockade of angiotensin AT1 receptors increases survival of obese Zucker rats. Eur. J. Pharmacol.534, 271–279 (2006). ArticleCASPubMed Google Scholar
Mizuno, M. et al. The effect of angiotensin II receptor blockade on an end-stage renal failure model of type 2 diabetes. J. Cardiovasc. Pharmacol.48, 135–142 (2006). ArticleCASPubMed Google Scholar
Amann, B., Tinzmann, R. & Angelkort, B. ACE inhibitors improve diabetic nephropathy through suppression of renal MCP-1. Diabetes Care26, 2421–2425 (2003). ArticleCASPubMed Google Scholar
Wada, T. et al. Gene therapy via blockade of monocyte chemoattractant protein-1 for renal fibrosis. J. Am. Soc. Nephrol.15, 940–948 (2004). ArticleCASPubMed Google Scholar
Umehara, H. et al. Fractalkine in vascular biology: from basic research to clinical disease. Arterioscler. Thromb. Vasc. Biol.24, 34–40 (2004). ArticleCASPubMed Google Scholar
Kikuchi, Y. et al. Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced diabetic kidneys. Nephron Exp. Nephrol.97, e17–e25 (2004). ArticleCASPubMed Google Scholar
Kikuchi, Y. et al. Advanced glycation end-product induces fractalkine gene upregulation in normal rat glomeruli. Nephrol. Dial. Transplant.20, 2690–2696 (2005). ArticleCASPubMed Google Scholar
Donadelli, R. et al. Protein overload induces fractalkine upregulation in proximal tubular cells through nuclear factor κB- and p38 mitogen-activated protein kinase-dependent pathways. J. Am. Soc. Nephrol.14, 2436–2446 (2003). ArticleCASPubMed Google Scholar
Segerer, S. et al. Expression of the fractalkine receptor (CX3CR1) in human kidney diseases. Kidney Int.62, 488–495 (2002). ArticleCASPubMed Google Scholar
Appay, V. & Rowland-Jones, S. L. RANTES: a versatile and controversial chemokine. Trends Immunol.22, 83–87 (2001). ArticleCASPubMed Google Scholar
Herder, C. et al. Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study. Diabetes55, 2340–2346 (2006). ArticleCASPubMed Google Scholar
Mezzano, S. et al. NF-κB activation and overexpression of regulated genes in human diabetic nephropathy. Nephrol. Dial. Transplant.19, 2505–2512 (2004). ArticleCASPubMed Google Scholar
Furuichi, K. et al. Distinct expression of CCR1 and CCR5 in glomerular and interstitial lesions of human glomerular diseases. Am. J. Nephrol.20, 291–299 (2000). ArticleCASPubMed Google Scholar
Choi, J. S., Choi, Y. J., Park, S. H., Kang, J. S. & Kang, Y. H. Flavones mitigate tumor necrosis factor-α-induced adhesion molecule upregulation in cultured human endothelial cells: role of nuclear factor-κB. J. Nutr.134, 1013–1019 (2004). ArticleCASPubMed Google Scholar
Sumagin, R. & Sarelius, I. H. TNF-α activation of arterioles and venules alters distribution and levels of ICAM-1 and affects leukocyte-endothelial cell interactions. Am. J. Physiol. Heart Circ. Physiol.291, H2116–H2125 (2006). ArticleCASPubMed Google Scholar
Sucosky, P., Balachandran, K., Elhammali, A., Jo, H. & Yoganathan, A. P. Altered shear stress stimulates upregulation of endothelial VCAM-1 and ICAM-1 in a BMP-4- and TGF-β1-dependent pathway. Arterioscler. Thromb. Vasc. Biol.29, 254–260 (2009). ArticleCASPubMed Google Scholar
Okada, S. et al. Intercellular adhesion molecule-1 deficient mice are resistant against renal injury after induction of diabetes. Diabetes52, 2586–2593 (2003). ArticleCASPubMed Google Scholar
Coimbra, T. M. et al. Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. Kidney Int.57, 167–182 (2000). ArticleCASPubMed Google Scholar
Lin, J. et al. Inflammation and progressive nephropathy in type 1 diabetes in the Diabetes Control and Complications Trial. Diabetes Care31, 2338–2343 (2008). ArticleCASPubMedPubMed Central Google Scholar
Ina, K. et al. Vascular cell adhesion molecule-1 expression in the renal interstitium of diabetic KKAy mice. Diabetes Res. Clin. Pract.44, 1–8 (1999). ArticleCASPubMed Google Scholar
Rubio-Guerra, A. F., Vargas-Robles, H., Lozano, J. J. & Escalante-Acosta, B. A. Correlation between circulating adhesion molecule levels and albuminuria in type-2 diabetic hypertensive patients. Kidney Blood Press. Res.32, 106–109 (2009). ArticleCASPubMed Google Scholar
Stehouwer, C. D. et al. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes51, 1157–1165 (2002). ArticleCASPubMed Google Scholar
Nasdala, I. et al. A transmembrane tight junction protein selectively expressed on endothelial cells and platelets. J. Biol. Chem.277, 16294–16303 (2002). ArticleCASPubMed Google Scholar
Hara, T., Ishida, T., Cangara, H. M. & Hirata, K. Endothelial cell-selective adhesion molecule regulates albuminuria in diabetic nephropathy. Microvasc. Res.77, 348–355 (2009). ArticleCASPubMed Google Scholar
Narumi, S., Onozato, M. L., Tojo, A., Sakamoto, S. & Tamatani, T. Tissue-specific induction of E-selectin in glomeruli is augmented following diabetes mellitus. Nephron89, 161–171 (2001). ArticleCASPubMed Google Scholar
Hirata, K. et al. Increased expression of selectins in kidneys of patients with diabetic nephropathy. Diabetologia41, 185–192 (1998). ArticleCASPubMed Google Scholar
Soedamah-Muthu, S. S. et al. Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated with micro- and macrovascular complications in type 1 diabetic patients. J. DiabetesComplications20, 188–195 (2006). Article Google Scholar
Lopes-Virella, M. F. et al. Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications. Diabetes Care31, 2006–2012 (2008). ArticleCASPubMedPubMed Central Google Scholar
Dandapani, S. V. et al. α-Actinin-4 is required for normal podocyte adhesion. J. Biol. Chem.282, 467–477 (2007). ArticleCASPubMed Google Scholar
Kimura, M. et al. Expression of alpha-actinin-4 in human diabetic nephropathy. Intern. Med.47, 1099–1106 (2008). ArticlePubMed Google Scholar
Pieper, G. M. & Riaz-ul-Haq. Activation of nuclear factor-κ-B in cultured endothelial cells by increased glucose concentration: prevention by calphostin C. J. Cardiovasc. Pharmacol.30, 528–532 (1997). ArticleCASPubMed Google Scholar
Yerneni, K. K., Bai, W., Khan, B. V., Medford, R. M. & Natarajan, R. Hyperglycemia-induced activation of nuclear transcription factor κB in vascular smooth muscle cells. Diabetes48, 855–864 (1999). ArticleCASPubMed Google Scholar
Gruden, G. et al. Mechanical stretch induces monocyte chemoattractant activity via an NF-kappaB-dependent monocyte chemoattractant protein-1-mediated pathway in human mesangial cells: inhibition by rosiglitazone. J. Am. Soc. Nephrol.16, 688–696 (2005). ArticleCASPubMed Google Scholar
Chuang, L.-Y. & Guh, J.-Y. Extracellular signals and intracellular pathways in diabetic nephropathy. Nephrology6, 165–172 (2001). ArticleCAS Google Scholar
Iwamoto, M., Mizuiri, S., Arita, M. & Hemmi, H. Nuclear factor-κB activation in diabetic rat kidney: evidence for involvement of P-selectin in diabetic nephropathy. Tohoku J. Exp. Med.206, 163–171 (2005). ArticleCASPubMed Google Scholar
Guijarro, C. & Egido, J. Transcription factor-κB (NF-κB) and renal disease. Kidney Int.59, 415–424 (2001). ArticleCASPubMed Google Scholar
Han, S. Y. et al. Spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. J. Am. Soc. Nephrol.17, 1362–1372 (2006). ArticleCASPubMed Google Scholar
Lee, F. T. et al. Interactions between angiotensin II and NF-κB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy. J. Am. Soc. Nephrol.15, 2139–2151 (2004). ArticleCASPubMed Google Scholar
Schmid, H. et al. Modular activation of nuclear factor-κB transcriptional programs in human diabetic nephropathy. Diabetes55, 2993–3003 (2006). ArticleCASPubMed Google Scholar
Hostetter, T. H. Prevention of end-stage renal disease due to type 2 diabetes. N. Engl. J. Med.345, 910–912 (2001). ArticleCASPubMed Google Scholar
Williams, M. E. & Tuttle, K. R. The next generation of diabetic nephropathy therapies: an update. Adv. Chronic Kidney Dis.12, 212–222 (2005). ArticlePubMed Google Scholar
Ohga, S. et al. Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-κB activation. Am. J. Physiol. Renal Physiol.292, F1141–F1150 (2007). ArticleCASPubMed Google Scholar
Ko, G. J. et al. Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. Nephrol. Dial. Transplant.23, 2750–2760 (2008). ArticleCASPubMed Google Scholar
Utimura, R. et al. Mycophenolate mofetil prevents the development of glomerular injury in experimental diabetes. Kidney Int.63, 209–216 (2003). ArticleCASPubMed Google Scholar
Zhang, Y. et al. Effects of mycophenolate mofetil, valsartan and their combined therapy on preventing podocyte loss in early stage of diabetic nephropathy in rats. Chin. Med. J. (Engl.)120, 988–995 (2007). ArticleCAS Google Scholar
Rodríguez-Iturbe, B., Quiroz, Y., Shahkarami, A., Li., Z. & Vaziri, N. D. Mycophenolate mofetil ameliorates nephropathy in the obese Zucker rat. Kidney Int.68, 1041–1047 (2005). ArticlePubMed Google Scholar
Moriwaki, Y. et al. Effect of TNF-α inhibition on urinary albumin excretion in experimental diabetic rats. Acta Diabetol.44, 215–218 (2007). ArticleCASPubMed Google Scholar
Han, J., Thompson, P. & Beutler, D. Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J. Exp. Med.172, 391–394 (1990). ArticleCASPubMed Google Scholar
Doherty, G. M., Jensen, J. C., Alexander, H. R., Buresh, C. M. & Norton, J. A. Pentoxifylline suppression of tumor necrosis factor gene transcription. Surgery110, 192–198 (1991). CASPubMed Google Scholar
Voisin, L. et al. Cytokine modulation by PX differently affects specific acute phase proteins during sepsis in rats. Am. J. Physiol.275, R1412–R1419 (1998). CASPubMed Google Scholar
Cooper, A., Mikhail, A., Lethbridge, M. W., Kemeny, D. M. & Macdougall, I. C. Pentoxifylline improves hemoglobin levels in patients with erythropoietin-resistant anemia in renal failure. J. Am. Soc. Nephrol.15, 1877–1882 (2004). ArticleCASPubMed Google Scholar
Bolick, D. T., Hatley, M. E., Srinivasan, S., Hedrick, C. C. & Nadler, J. L. Lisofylline, a novel antiinflammatory compound, protects mesangial cells from hyperglycemia- and angiotensin II-mediated extracellular matrix deposition. Endocrinology144, 5227–5231 (2003). ArticleCASPubMed Google Scholar
Dávila-Esqueda, M. E., Vertiz-Hernández, A. A. & Martínez-Morales, F. Comparative analysis of the renoprotective effects of pentoxifylline and vitamin E on streptozotocin-induced diabetes mellitus. Ren. Fail.27, 115–122 (2005). ArticlePubMed Google Scholar
Blagosklonnaia, IaV., Marnedov, R., Kozlov, V. V., Emanuél, V. L. & Kudriashova, M. I. Effect of trental on indices of kidney function in diabetes mellitus [Russian]. Probl. Endokrinol. (Mosk.)28, 3–8 (1982). Google Scholar
Solerte, S. B. et al. Pentoxifylline, albumin excretion rate and proteinuria in type I and type II diabetic patients with microproteinuria. Results of a short-term randomized study. Acta Diabetol. Lat.23, 171–177 (1986). ArticleCASPubMed Google Scholar
Tripathy, K., Praskash, J., Appaiha, D. & Srivastava, P. K. Pentoxifylline in management of proteinuria in diabetic nephropathy. Nephron64, 641–642 (1993). Article Google Scholar
Guerrero-Romero, F. et al. Pentoxifylline reduces proteinuria in insulin-dependent and non insulin-dependent diabetic patients. Clin. Nephrol.43, 116–121 (1995). CASPubMed Google Scholar
Gorson, D. M. Reduction of macroalbuminuria with pentoxifylline in diabetic nephropathy. Report of three cases. Diabetes Care21, 2190–2191 (1998). ArticleCASPubMed Google Scholar
Navarro, J. F. & Mora, C. Antiproteinuric effect of pentoxifylline in patients with diabetic nephropathy. Diabetes Care22, 1006–1008 (1999). ArticleCASPubMed Google Scholar
Navarro, J. F. et al. Urinary protein excretion and serum tumor necrosis factor in diabetic patients with advanced renal failure: effects of pentoxifylline administration. Am. J. Kidney Dis.33, 458–463 (1999). ArticleCASPubMed Google Scholar
Navarro, J. F., Mora, C., Muros, M., Maca, M. & Garca, J. Effects of pentoxifylline administration on urinary _N_-acetyl-β-glucosaminidase excretion in type 2 diabetic patients: a short-term, prospective, randomized study. Am. J. Kidney Dis.42, 264–270 (2003). ArticleCASPubMed Google Scholar
Rodriguez-Morán, M. et al. Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: a double-blind, placebo-controlled randomized trial. Clin. Nephrol.66, 3–10 (2006). ArticlePubMed Google Scholar
Leyva-Jiménez, R. et al. Effect of pentoxifylline on the evolution of diabetic nephropathy [Spanish]. Med. Clin. (Barc.)132, 772–778 (2009). Article Google Scholar
Navarro, J. F., Mora, C., Muros, M. & García, J. Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial. J. Am. Soc. Nephrol.16, 2119–2126 (2005). ArticleCASPubMed Google Scholar
Roozbeh, J. et al. Captopril and combination therapy of captopril and pentoxifylline in reducing proteinuria in diabetic nephropathy. Ren. Fail.32, 172–178 (2010). ArticleCASPubMed Google Scholar
McCormick, B. B. et al. The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis. Am. J. Kidney Dis.52, 454–463 (2008). ArticleCASPubMed Google Scholar
Navarro-González, J. F. et al. Pentoxifylline for renoprotection in diabetic nephropathy: the PREDIAN study. Rationale and basal results. J. Diabetes Complications doi:10.1016/j.jdiacomp.2010.09.003.