The renal metallothionein expression profile is altered in human lupus nephritis
Tóm tắt
Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT-I+II expression profile is altered during lupus nephritis. Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means of standard statistical methods. Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median number of proximal tubules displaying this MT expression pattern per high-power microscope field (40× magnification), was positively correlated to the creatinine clearance in the lupus nephritis cohort (P = 0.01). Furthermore, a tubular MT score below the median value of the cohort emerged as a significant predictor of a poor renal outcome in renal survival analyses. Thus, patients with a tubular MT score < 1.0 had a 6.2-times higher risk of developing end-stage renal disease than patients with a tubular MT score ≥ 1.0 (P = 0.03). Lupus nephritis is associated with significant alterations in renal MT-I+II expression. Our data indicate that important prognostic information can be deduced from the renal MT-I+II expression profile in systemic lupus erythematosus patients with nephritis.
Tài liệu tham khảo
Cameron JS: Lupus nephritis. J Am Soc Nephrol. 1999, 10: 413-424.
MacGowan JR, Ellis S, Griffiths M, Isenberg DA: Retrospective analysis of outcome in a cohort of patients with lupus nephritis treated between 1977 and 1999. Rheumatology (Oxford). 2002, 41: 981-987. 10.1093/rheumatology/41.9.981.
Martins L, Rocha G, Rodrigues A, Santos J, Vasconcelos C, Correia J, Farinha F, Almeida I, Barbosa P, Guimaraes S: Lupus nephritis: a retrospective review of 78 cases from a single center. Clin Nephrol. 2002, 57: 114-119.
Faurschou M, Starklint H, Halberg P, Jacobsen S: Prognostic factors in lupus nephritis: diagnostic and therapeutic delay increases the risk of terminal renal failure. J Rheumatol. 2006, 33: 1563-1569.
Davidson A, Aranow C: Pathogenesis and treatment of systemic lupus erythematosus nephritis. Curr Opin Rheumatol. 2006, 18: 468-475.
Penkowa M: Metallothioneins are multipurpose neuroprotectants during brain pathology. FEBS J. 2006, 273: 1857-1870. 10.1111/j.1742-4658.2006.05207.x.
Carrasco J, Penkowa M, Hadberg H, Molinero A, Hidalgo J: Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice. Eur J Neurosci. 2000, 12: 2311-2322. 10.1046/j.1460-9568.2000.00128.x.
Giralt M, Penkowa M, Hernandez J, Molinero A, Carrasco J, Lago N, Camats J, Campbell IL, Hidalgo J: Metallothionein-1+2 deficiency increases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin 6. Neurobiol Dis. 2002, 9: 319-338. 10.1006/nbdi.2002.0480.
Penkowa M, Florit S, Giralt M, Quintana A, Molinero A, Carrasco J, Hidalgo J: Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures. J Neurosci Res. 2005, 79: 522-534. 10.1002/jnr.20387.
Li X, Chen H, Epstein PN: Metallothionein protects islets from hypoxia and extends islet graft survival by scavenging most kinds of reactive oxygen species. J Biol Chem. 2004, 279: 765-771. 10.1074/jbc.M307907200.
Youn J, Lynes MA: Metallothionein-induced suppression of cytotoxic T lymphocyte function: an important immunoregulatory control. Toxicol Sci. 1999, 52: 199-208. 10.1093/toxsci/52.2.199.
Lynes MA, Borghesi LA, Youn J, Olson EA: Immunomodulatory activities of extracellular metallothionein. I. Metallothionein effects on antibody production. Toxicology. 1993, 85: 161-177. 10.1016/0300-483X(93)90040-Y.
Nartey NO, Banerjee D, Cherian MG: Immunohistochemical localization of metallothionein in cell nucleus and cytoplasm of fetal human liver and kidney and its changes during development. Pathology. 1987, 19: 233-238. 10.3109/00313028709066555.
Mididoddi S, McGuirt JP, Sens MA, Todd JH, Sens DA: Isoform-specific expression of metallothionein mRNA in the developing and adult human kidney. Toxicol Lett. 1996, 85: 17-27. 10.1016/0378-4274(96)03632-6.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25: 1271-1277. 10.1002/art.1780251101.
Vitali C, Bencivelli W, Isenberg DA, Smolen JS, Snaith ML, Sciuto M, d'Ascanio A, Bombardieri S: Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. I. A descriptive analysis of 704 European lupus patients. European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol. 1992, 10: 527-539.
Churg J, Sobin LH: Renal disease: classification and atlas of glomerular disease. Tokyo: Igaku-Shoin. 1982, 127-131.
Austin HA, Muenz LR, Joyce KM, Antonovych TA, Kullick ME, Klippel JH, Decker JL, Balow JE: Prognostic factors in lupus nephritis. Contribution of renal histologic data. Am J Med. 1983, 75: 382-391. 10.1016/0002-9343(83)90338-8.
Penkowa M, Giralt M, Carrasco J, Hadberg H, Hidalgo J: Impaired inflammatory response and increased oxidative stress and neurodegeneration after brain injury in interleukin-6-deficient mice. Glia. 2000, 32: 271-285. 10.1002/1098-1136(200012)32:3<271::AID-GLIA70>3.0.CO;2-5.
Penkowa M, Hidalgo J, Moos T: Increased astrocytic expression of metallothioneins I + II in brainstem of adult rats treated with 6-aminonicotinamide. Brain Res. 1997, 774: 256-259. 10.1016/S0006-8993(97)81716-7.
Gasull T, Rebollo DV, Romero B, Hidalgo J: Development of a competitive double antibody radioimmunoassay for rat metallothionein. J Immunoassay. 1993, 14: 209-225. 10.1080/15321819308019851.
Penkowa M, Moos T, Carrasco J, Hadberg H, Molinero A, Bluethmann H, Hidalgo J: Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice. Glia. 1999, 25: 343-357. 10.1002/(SICI)1098-1136(19990215)25:4<343::AID-GLIA4>3.0.CO;2-V.
Penkowa M, Espejo C, Ortega-Aznar A, Hidalgo J, Montalban X, Martinez Caceres EM: Metallothionein expression in the central nervous system of multiple sclerosis patients. Cell Mol Life Sci. 2003, 60: 1258-1266.
Wang Y, Chen J, Chen L, Tay YC, Rangan GK, Harris DC: Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein. J Am Soc Nephrol. 1997, 8: 1537-1545.
Zoja C, Donadelli R, Colleoni S, Figliuzzi M, Bonazzola S, Morigi M, Remuzzi G: Protein overload stimulates RANTES production by proximal tubular cells depending on NF-kappa B activation. Kidney Int. 1998, 53: 1608-1615. 10.1046/j.1523-1755.1998.00905.x.
Tang S, Leung JC, Abe K, Chan KW, Chan LY, Chan TM, Lai KN: Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. J Clin Invest. 2003, 111: 515-527.
Tang S, Sheerin NS, Zhou W, Brown Z, Sacks SH: Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells. J Am Soc Nephrol. 1999, 10: 69-76.
Abbate M, Zoja C, Rottoli D, Corna D, Tomasoni S, Remuzzi G: Proximal tubular cells promote fibrogenesis by TGF-beta1-mediated induction of peritubular myofibroblasts. Kidney Int. 2002, 61: 2066-2077. 10.1046/j.1523-1755.2002.00380.x.
Benigni A, Caroli C, Longaretti L, Gagliardini E, Zoja C, Galbusera M, Moioli D, Romagnani P, Tincani A, Andreoli L, Remuzzi G: Involvement of renal tubular Toll-like receptor 9 in the development of tubulointerstitial injury in systemic lupus. Arthritis Rheum. 2007, 56: 1569-1578. 10.1002/art.22524.
Daniel L, Sichez H, Giorgi R, Dussol B, Figarella-Branger D, Pellissier JF, Berland Y: Tubular lesions and tubular cell adhesion molecules for the prognosis of lupus nephritis. Kidney Int. 2001, 60: 2215-2221. 10.1046/j.1523-1755.2001.00055.x.
Illei GG, Lipsky PE: Biomarkers in systemic lupus erythematosus. Curr Rheumatol Rep. 2004, 6: 382-390. 10.1007/s11926-004-0013-4.
Wu T, Xie C, Wang HW, Zhou XJ, Schwartz N, Calixto S, Mackay M, Aranow C, Putterman C, Mohan C: Elevated urinary VCAM-1, P-selectin, soluble TNF receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis. J Immunol. 2007, 179: 7166-7175.
Derksen RH, Hene RJ, Kater L: The long-term clinical outcome of 56 patients with biopsy-proven lupus nephritis followed at a single center. Lupus. 1992, 1: 97-103. 10.1177/096120339200100207.
Ravinal RC, Costa RS, Coimbra TM, Pastorello MT, Coelho EB, Dantas M, dos RM: Classes, activity and chronicity indices, and alpha-smooth muscle actin expression as prognostic parameters in lupus nephritis outcome. Lupus. 2002, 11: 82-87. 10.1191/0961203302lu153oa.
Austin HA, Boumpas DT, Vaughan EM, Balow JE: High-risk features of lupus nephritis: importance of race and clinical and histological factors in 166 patients. Nephrol Dial Transplant. 1995, 10: 1620-1628.
Austin HA, Boumpas DT, Vaughan EM, Balow JE: Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int. 1994, 45: 544-550. 10.1038/ki.1994.70.
Conlon PJ, Fischer CA, Levesque MC, Smith SR, St Clair EW, Allen NB, Fleming JA, Howell DN: Clinical, biochemical and pathological predictors of poor response to intravenous cyclophosphamide in patients with proliferative lupus nephritis. Clin Nephrol. 1996, 46: 170-175.
Klaassen CD, Liu J, Choudhuri S: Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol. 1999, 39: 267-294. 10.1146/annurev.pharmtox.39.1.267.
Ogra Y, Suzuki KT: Nuclear trafficking of metallothionein: possible mechanisms and current knowledge. Cell Mol Biol (Noisy-le-grand). 2000, 46: 357-365.
Chung RS, West AK: A role for extracellular metallothioneins in CNS injury and repair. Neuroscience. 2004, 123: 595-599. 10.1016/j.neuroscience.2003.10.019.