Article information
No existen estrategias terapéuticas y fisiopatológicas para el fracaso renal agudo (FRA), por lo que los niveles de mortalidad continúan siendo elevados. Además, la enfermedad renal crónica (ERC) predispone a sufrir FRA y el FRA, a su vez, contribuye a que la ERC avance. Recientemente, una estrategia transcriptómica reveló una relación entre el FRA, la inflamación y la regulación del envejecimiento. Un análisis transcriptómico de modelos experimentales de FRA reveló un aumento de la expresión renal de Fn14 y la quimiocina transmembrana CXCL16, así como un descenso en la expresión de la hormona Klotho antienvejecimiento secretada por el riñón. Fn14 es el receptor de la citoquina tumor necrosis factor-like weak inducer of apoptosis (TWEAK), miembro de la superfamilia de factor de necrosis tumoral. En los riñones con FRA, existía una correlación positiva entre Fn14 y la expresión de ARNm de CXCL16 y una correlación inversa entre Fn14 y el ARNm de Klotho. El lugar donde se da la expresión in vivo de Fn14, CXCL16 y Klotho es las células tubulares. La investigación en las relaciones entre estas tres moléculas reveló que la activación de Fn14 por TWEAK provocó la inflamación mediante la secreción de quimiocinas como la CXCL16 en células tubulares, tanto en cultivo como in vivo. Además, la activación de Fn14 por TWEAK disminuyó la expresión de ARNm de Klotho y de proteína, en cultivo y in vivo. Curiosamente, tanto la activación TWEAK de la trascripción de ARNm de CXCL16 y la supresión de la trascripción de ARNm de Klotho estuvieron mediadas por el factor de transcripción NF-kB. Como conclusión, la unión de TWEAK y Fn14 es un elemento clave en promover de la activación mediada por NF-kB de las vías de inflamación y en la supresión de las vías antiinflamatorias y antienvejecimiento. Esta información puede influir en las futuras estrategias terapéuticas para el FRA y la inflamación/envejecimiento.
Palabras clave:
Enfermedad renal crónica
Palabras clave:
Envejecimiento
Palabras clave:
Fracaso renal agudo
Palabras clave:
Klotho
Palabras clave:
TWEAK
Palabras clave:
Inflamación
There are no pathophysiolgical therapeutic approaches to acute kidney injury (AKI) and the mortality remains high. In addition chronic kidney disease (CKD) predisposes to AKI and AKI contributes to progression of CKD. Recently a transcriptomics approach unveiled a relationship between AKI, inflammation and the regulation of ageing. A transcriptomics analysis of experimental AKI revealed increased kidney expression of Fn14 and transmembrane chemokine CXCL16, as well as a decreased expression of the kidney-secreted anti-ageing hormone Klotho. Fn14 is the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily. In AKI kidneys there was a positive correlation between Fn14 and CXCL16 mRNA expression and an inverse correlation between Fn14 and Klotho mRNA. Tubular cells were the site of Fn14, CXCL16 and Klotho expression in vivo. Research on the relationships between these three molecules disclosed that TWEAK activation of Fn14 promoted inflammation through secretion of chemokines such as CXL16 in tubular cells in culture and in vivo. Furthermore, TWEAK activation of Fn14 decreased expression of Klotho mRNA and protein in culture and in vivo. Interestingly, both TWEAK activation of CXCL16 mRNA transcription and suppression of Klotho mRNA transcription were mediated by the NFκB transcription factor. In conclusion, TWEAK engagement of Fn14 is a central event promoting NFκB-mediated activation of inflammation pathways and suppression of anti-inflammatory/anti-ageing pathways. This information may influence future therapeutic approaches to AKI and inflammation/aging.
Keywords:
Chronic kidney disease
Keywords:
Aging
Keywords:
Acute kidney injury
Keywords:
Klotho
Keywords:
TWEAK
Keywords:
Inflammation
Full text is only aviable in PDF
Bibliografía
[1]
Chawla LS, Kimmel PL. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int 2012;82(5):516-24. [Pubmed]
[2]
Hu MC, Moe OW. Klotho as a potential biomarker and therapy for acute kidney injury. Nat Rev Nephrol 2012;8:423-9. [Pubmed]
[3]
Hu MC, Shi M, Zhang J, Quiñones H, Griffith C, Kuro-o M, et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 2011;22:124-36. [Pubmed]
[4]
Spasovski G, Ortiz A, Vanholder R, El NM. Proteomics in chronic kidney disease: The issues clinical nephrologists need an answer for. Proteomics Clin Appl 2011;5:233-40. [Pubmed]
[5]
Benito-Martin A, Ucero AC, Santamaria B, Lorz C, Kretzler M, Rastaldi MP, et al. [Transcriptomics illustrate a deadly TRAIL to diabetic nephropathy]. Nefrologia 2009;29:13-9. [Pubmed]
[6]
Sanchez-Nino MD, Benito-Martin A, Ortiz A. New paradigms in cell death in human diabetic nephropathy. Kidney Int 2010;78:737-44. [Pubmed]
[7]
Moreno JA, Izquierdo MC, Sanchez-Nino MD, Suarez-Alvarez B, Lopez-Larrea C, Jakubowski A, et al. The inflammatory cytokines TWEAK and TNFalpha reduce renal klotho expression through NFkappaB. J Am Soc Nephrol 2011;22:1315-25. [Pubmed]
[8]
Izquierdo MC, Sanz AB, Mezzano S, Blanco J, Carrasco S, Sanchez-Niño MD, et al. TWEAK (tumor necrosis factor-like weak inducer of apoptosis) activates CXCL16 expression during renal tubulointerstitial inflammation. Kidney Int 2012;81:1098-107. [Pubmed]
[9]
Sanchez-Niño MD, Sanz AB, Lorz C, Gnirke A, Rastaldi MP, Nair V, et al. BASP1 promotes apoptosis in diabetic nephropathy. J Am Soc Nephrol 2010;21:610-21. [Pubmed]
[10]
Sanchez-Niño MD, Sanz AB, Ihalmo P, Lassila M, Holthofer H, Mezzano S, et al. The MIF receptor CD74 in diabetic podocyte injury. J Am Soc Nephrol 2009;20:353-62. [Pubmed]
[11]
Lorz C, Benito-Martín A, Boucherot A, Ucero AC, Rastaldi MP, Henger A, et al. The death ligand TRAIL in diabetic nephropathy. J Am Soc Nephrol 2008;19:904-14. [Pubmed]
[12]
Sanchez-Niño MD, Sanz AB, Sanchez-Lopez E, Ruiz-Ortega M, Benito-Martin A, Saleem MA, et al. HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II. Lab Invest 2012;92:32-45. [Pubmed]
[13]
Chicheportiche Y, Bourdon PR, Xu H, Hsu YM, Scott H, Hession C, et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem 1997;272:32401-10. [Pubmed]
[14]
Sanz AB, Sanchez-Niño MD, Ortiz A. TWEAK, a multifunctional cytokine in kidney injury. Kidney Int 2011;80:708-18. [Pubmed]
[15]
Sanz AB, Sanchez-Niño MD, Izquierdo MC, Moreno JA, Ucero AC, Benito-Martín A, et al. [TWEAK, the facilitator of acute kidney injury]. Nefrologia 2008;28:587-92. [Pubmed]
[16]
Ortiz A, Bustos C, Alonso J, Alcázar R, López-Armada MJ, Plaza JJ, et al. Involvement of tumor necrosis factor-alpha in the pathogenesis of experimental and human glomerulonephritis. Adv Nephrol Necker Hosp 1995;24:53-77. [Pubmed]
[17]
Ortiz A, Lorz C, Egido J. The Fas ligand/Fas system in renal injury. Nephrol Dial Transplant 1999;14:1831-4. [Pubmed]
[18]
Sanchez-Niño MD, Benito-Martin A, Goncalves S, Sanz AB, Ucero AC et al. TNF superfamily: a growing saga of kidney injury modulators. Mediators Inflamm 2010;2010. pii: 182958.
[19]
Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001;104:487-501. [Pubmed]
[20]
Bodmer JL, Schneider P, Tschopp J. The molecular architecture of the TNF superfamily. Trends Biochem Sci 2002;27:19-26. [Pubmed]
[21]
Marsters SA, Sheridan JP, Pitti RM, Brush J, Goddard A, Ashkenazi A. Identification of a ligand for the death-domain-containing receptor Apo3. Curr Biol 1998;8:525-8. [Pubmed]
[22]
De Ketelaere A, Vermeulen L, Vialard J, Van De Weyer I, Van Wauwe J, Haegeman G, et al. Involvement of GSK-3beta in TWEAK-mediated NF-kappaB activation. FEBS Lett 2004;566:60-4. [Pubmed]
[23]
Baxter FO, Came PJ, Abell K, Kedjouar B, Huth M, Rajewsky K, et al. IKKbeta/2 induces TWEAK and apoptosis in mammary epithelial cells. Development 2006;133:3485-94. [Pubmed]
[24]
Brown SA, Ghosh A, Winkles JA. Full-length, membrane-anchored TWEAK can function as a juxtacrine signaling molecule and activate the NF-kappaB pathway. J Biol Chem 2010;285:17432-41. [Pubmed]
[25]
Nakayama M, Kayagaki N, Yamaguchi N, Okumura K, Yagita H. Involvement of TWEAK in interferon gamma-stimulated monocyte cytotoxicity. J Exp Med 2000;192:1373-80. [Pubmed]
[26]
Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov 2008;7:411-25. [Pubmed]
[27]
Roos C, Wicovsky A, Muller N, Salzmann S, Rosenthal T, Kalthoff H, et al. Soluble and transmembrane TNF-like weak inducer of apoptosis differentially activate the classical and noncanonical NF-kappa B pathway. J Immunol 2010;185:1593-605. [Pubmed]
[28]
Wiley SR, Cassiano L, Lofton T, vis-Smith T, Winkles JA, Lindner V, et al. A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Immunity 2001;15:837-46. [Pubmed]
[29]
Feng SL, Guo Y, Factor VM, Thorgeirsson SS, Bell DW, Testa JR, et al. The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas. Am J Pathol 2000;156:1253-61. [Pubmed]
[30]
Meighan-Mantha RL, Hsu DK, Guo Y, Brown SA, Feng SL, Peifley K, et al. The mitogen-inducible Fn14 gene encodes a type I transmembrane protein that modulates fibroblast adhesion and migration. J Biol Chem 1999;274:33166-76. [Pubmed]
[31]
Brown SA, Richards CM, Hanscom HN, Feng SL, Winkles JA. The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation. Biochem J 2003;371:395-403. [Pubmed]
[32]
Bover LC, Cardó-Vila M, Kuniyasu A, Sun J, Rangel R, Takeya M, et al. A previously unrecognized protein-protein interaction between TWEAK and CD163: potential biological implications. J Immunol 2007;178:8183-94. [Pubmed]
[33]
Moreno JA, Muñoz-García B, Martín-Ventura JL, Madrigal-Matute J, Orbe J, Páramo JA, et al. The CD163-expressing macrophages recognize and internalize TWEAK: potential consequences in atherosclerosis. Atherosclerosis 2009;207:103-10. [Pubmed]
[34]
Jakubowski A, Ambrose C, Parr M, Lincecum JM, Wang MZ, Zheng TS, et al. TWEAK induces liver progenitor cell proliferation. J Clin Invest 2005;115:2330-40. [Pubmed]
[35]
Lynch CN, Wang YC, Lund JK, Chen YW, Leal JA, Wiley SR, et al. TWEAK induces angiogenesis and proliferation of endothelial cells. J Biol Chem 1999;274:8455-9. [Pubmed]
[36]
Maecker H, Varfolomeev E, Kischkel F, Lawrence D, LeBlanc H, Lee W, et al. TWEAK attenuates the transition from innate to adaptive immunity. Cell 2005;123:931-44. [Pubmed]
[37]
Nakayama M, Harada N, Okumura K, Yagita H. Characterization of murine TWEAK and its receptor (Fn14) by monoclonal antibodies. Biochem Biophys Res Commun 2003;306:819-25. [Pubmed]
[38]
Naumann M, Nieters A, Hatada EN, Scheidereit C. NF-kappa B precursor p100 inhibits nuclear translocation and DNA binding of NF-kappa B/rel-factors. Oncogene 1993;8:2275-81. [Pubmed]
[39]
Tran NL, McDonough WS, Savitch BA, Sawyer TF, Winkles JA, Berems ME, et al. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)-fibroblast growth factor-inducible 14 (Fn14) signaling system regulates glioma cell survival via NFkappaB pathway activation and BCL-XL/BCL-W expression. J Biol Chem 2005;280:3483-92. [Pubmed]
[40]
Mittal A, Bhatnagar S, Kumar A, Lach-Trifilieff E, Wauters S, Li H, et al. The TWEAK-Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice. J Cell Biol 2010;188:833-49. [Pubmed]
[41]
Wang D, Fung JN, Tuo Y, Hu L, Chen C. TWEAK/Fn14 promotes apoptosis of human endometrial cancer cells via caspase pathway. Cancer Lett 2010;294:91-100. [Pubmed]
[42]
Novoyatleva T, Diehl F, van Amerongen MJ, Patra C, Ferrazzi F, Bellazzi R, et al. TWEAK is a positive regulator of cardiomyocyte proliferation. Cardiovasc Res 2010;85:681-90. [Pubmed]
[43]
Tiller G, Fischer-Posovszky P, Laumen H, Finck A, Skurk T, Keuper M, et al. Effects of TWEAK (TNF superfamily member 12) on differentiation, metabolism, and secretory function of human primary preadipocytes and adipocytes. Endocrinology 2009;150:5373-83. [Pubmed]
[44]
Desplat-Jégo S, Creidy R, Varriale S, Allaire N, Luo Y, Bernard D, et al. Anti-TWEAK monoclonal antibodies reduce immune cell infiltration in the central nervous system and severity of experimental autoimmune encephalomyelitis. Clin Immunol 2005;117:15-23. [Pubmed]
[45]
Dohi T, Borodovsky A, Wu P, Shearstone JR, Kawashima R, Runkel L, et al. TWEAK/Fn14 pathway: a nonredundant role in intestinal damage in mice through a TWEAK/intestinal epithelial cell axis. Gastroenterology 2009;136:912-23. [Pubmed]
[46]
Muñoz-García B, Moreno JA, López-Franco O, Sanz AB, Martín-Ventura JL, Blanco J, et al. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice. Arterioscler Thromb Vasc Biol 2009;29:2061-8. [Pubmed]
[47]
Muñoz-García B, Madrigal-Matute J, Moreno JA, Martín-Ventura JL, López-Franco O, Sastre C, et al. TWEAK-Fn14 interaction enhances plasminogen activator inhibitor 1 and tissue factor expression in atherosclerotic plaques and in cultured vascular smooth muscle cells. Cardiovasc Res 2011;89:225-33. [Pubmed]
[48]
Haile WB, Echeverry R, Wu J, Yepes M. The interaction between tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 promotes the recruitment of neutrophils into the ischemic brain. J Cereb Blood Flow Metab 2010;30:1147-56. [Pubmed]
[49]
Tirnitz-Parker JE, Viebahn CS, Jakubowski A, Klopcic BR, Olynyk JK, Yeoh GC, et al. Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells. Hepatology 2010;52:291-302. [Pubmed]
[50]
Sanz AB, Sanchez-Niño MD, Izquierdo MC, Jakubowski A, Justo P, Blanco-Colio LM, et al. Tweak induces proliferation in renal tubular epithelium: a role in uninephrectomy induced renal hyperplasia. J Cell Mol Med 2009;13:3329-42. [Pubmed]
[51]
Justo P, Sanz AB, Sanchez-Niño MD, Winkles JA, Lorz C, Egido J, et al. Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney Int 2006;70:1750-8. [Pubmed]
[52]
Sanz AB, Sanchez-Niño MD, Ramos AM, Moreno JA, Santamaria B, Ruiz-Ortega M, et al. NF-kappaB in renal inflammation. J Am Soc Nephrol 2010;21:1254-62. [Pubmed]
[53]
Sanz AB, Sanchez-Niño MD, Izquierdo MC, Jakubowski A, Justo P, Blanco-Colio LM, et al. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21. PLoS One 2010;5:e8955. [Pubmed]
[54]
Sanz AB, Justo P, Sanchez-Niño MD, Blanco-Colio LM, Winkles JA, Kreztler M, et al. The cytokine TWEAK modulates renal tubulointerstitial inflammation. J Am Soc Nephrol 2008;19:695-703. [Pubmed]
[55]
Hotta K, Sho M, Yamato I, Shimada K, Harada H, Akahori T, et al. Direct targeting of fibroblast growth factor-inducible 14 protein protects against renal ischemia reperfusion injury. Kidney Int 2011;79:179-88. [Pubmed]
[56]
Sanz AB, Sanchez-Niño MD, Izquierdo MC, Jakubowski A, Justo P, Blanco-Colio LM, et al. Tweak induces proliferation in renal tubular epithelium: a role in uninephrectomy induced renal hyperplasia. J Cell Mol Med 2009;13:3329-42. [Pubmed]
[57]
Carrero JJ, Ortiz A, Qureshi AR, Martín-Ventura JL, Bárány P, Heimbürger O, et al. Additive effects of soluble TWEAK and inflammation on mortality in hemodialysis patients. Clin J Am Soc Nephrol 2009;4:110-8. [Pubmed]
[58]
Blanco-Colio LM, Martín-Ventura JL, Muñoz-García B, Orbe J, Páramo JA, Michel JB, et al. Identification of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) as a possible biomarker of subclinical atherosclerosis. Arterioscler Thromb Vasc Biol 2007;27:916-22. [Pubmed]
[59]
Yilmaz MI, Sonmez A, Ortiz A, Saglam M, Kilic S, Eyileten T, et al. Soluble TWEAK and PTX3 in nondialysis CKD patients: impact on endothelial dysfunction and cardiovascular outcomes. Clin J Am Soc Nephrol 2011;6:785-92. [Pubmed]
[60]
Yilmaz MI, Carrero JJ, Ortiz A, Martín-Ventura JL, Sonmez A, Saglam M, et al. Soluble TWEAK plasma levels as a novel biomarker of endothelial function in patients with chronic kidney disease. Clin J Am Soc Nephrol 2009;4:1716-23. [Pubmed]
[61]
Ortiz A, Sanz AB, Muñoz GB, Moreno JA, Sánchez Niño MD, Martín-Ventura JL, et al. Considering TWEAK as a target for therapy in renal and vascular injury. Cytokine Growth Factor Rev 2009;20:251-58.
[62]
Gomez-Chiarri M, Ortiz A, Seron D, Gonzalez E, Egido J. The intercrine superfamily and renal disease. Kidney Int Suppl 1993;39:S81-S85. [Pubmed]
[63]
González-Cuadrado S, Bustos C, Ruiz-Ortega M, Ortiz A, Guijarro C. Egido J. Expression of leucocyte chemoattractants by interstitial renal fibroblasts: up-regulation by drugs associated with interstitial fibrosis. Clin Exp Immunol 1996;106:518-22. [Pubmed]
[66]
Moreno JA, Moreno S, Rubio-Navarro A, Sastre C, Blanco-Colio LM, Gómez-Guerrero C, et al. Targeting chemokines in proteinuria-induced renal disease. Expert Opin Ther Targets 2012;16:833-45. [Pubmed]
[67]
Singbartl K, Ley K. Leukocyte recruitment and acute renal failure. J Mol Med 2004;82:91-101. [Pubmed]
[68]
Olson TS, Ley K. Chemokines and chemokine receptors in leukocyte trafficking. Am J Physiol Regul Integr Comp Physiol 2002;283:R7-28. [Pubmed]
[69]
Ludwig A, Weber C. Transmembrane chemokines: versatile 'special agents' in vascular inflammation. Thromb Haemost 2007;97:694-703. [Pubmed]
[70]
Koziolek MJ, Vasko R, Bramlage C, Muller GA, Strutz F. The CX(3)C-chemokine fractalkine in kidney diseases. Mini Rev Med Chem 2009;9:1215-28. [Pubmed]
[71]
Schwartz N, Rubinstein T, Burkly LC, Collins CE, Blanco I, Su L, et al. Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study. Arthritis Res Ther 2009;11 R143.
[72]
Wu T, Xie C, Wang HW, Zhou XJ, Schwartz N, Calixto S, et al. 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;179:7166-75. [Pubmed]
[73]
Matloubian M, David A, Engel S, Ryan JE, Cyster JG. A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 2000;1:298-304. [Pubmed]
[74]
Shimaoka T, Kume N, Minami M, Hayashida K, Kataoka H, Kita T, et al. Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages. J Biol Chem 2000;275:40663-6. [Pubmed]
[75]
Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, et al. A new class of membrane-bound chemokine with a CX3C motif. Nature 1997;385:640-4. [Pubmed]
[76]
Pan Y, Lloyd C, Zhou H, Dolich S, Deeds J, Gonzalo JA, et al. Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation. Nature 1997;387:611-7. [Pubmed]
[77]
Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, et al. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 1997;91:521-30. [Pubmed]
[78]
Shimaoka T, Nakayama T, Fukumoto N, Kume N, Takahashi S, Yamaguchi J, et al. Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J Leukoc Biol 2004;75:267-74. [Pubmed]
[79]
Schramme A, Abdel-Bakky MS, Kampfer-Kolb N, Pfeilschifter J, Gutwein P. The role of CXCL16 and its processing metalloproteinases ADAM10 and ADAM17 in the proliferation and migration of human mesangial cells. Biochem Biophys Res Commun 2008;370:311-6. [Pubmed]
[80]
Hattermann K, Ludwig A, Gieselmann V, Held-Feindt J, Mentlein R. The chemokine CXCL16 induces migration and invasion of glial precursor cells via its receptor CXCR6. Mol Cell Neurosci 2008;39:133-41. [Pubmed]
[81]
Dahl CP, Husberg C, Gullestad L, Waehre A, Damås JK, Vinge LE, et al. Increased production of CXCL16 in experimental and clinical heart failure: a possible role in extracellular matrix remodeling. Circ Heart Fail 2009;2:624-32. [Pubmed]
[82]
Huang Y, Zhu XY, Du MR, Wu X, Wang MY, Li DJ, et al. Chemokine CXCL16, a scavenger receptor, induces proliferation and invasion of first-trimester human trophoblast cells in an autocrine manner. Hum Reprod 2006;21:1083-91. [Pubmed]
[83]
Zhuge X, Murayama T, Arai H, Yamauchi R, Tanaka M, Shimaoka T, et al. CXCL16 is a novel angiogenic factor for human umbilical vein endothelial cells. Biochem Biophys Res Commun 2005;331:1295-300. [Pubmed]
[84]
Chandrasekar B, Bysani S, Mummidi S. CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation. J Biol Chem 2004;279:3188-96.
[85]
Deng L, Chen N, Li Y, Zheng H, Lei Q. CXCR6/CXCL16 functions as a regulator in metastasis and progression of cancer. Biochim Biophys Acta 2010;1806:42-9. [Pubmed]
[86]
Schramme A, Abdel-Bakky MS, Gutwein P, Obermuller N, Baer PC, Hauser IA, et al. Characterization of CXCL16 and ADAM10 in the normal and transplanted kidney. Kidney Int 2008;74:328-38. [Pubmed]
[87]
Gutwein P, Abdel-Bakky MS, Schramme A, Doberstein K, Kämpfer-Kolb N, Amann K, et al. CXCL16 is expressed in podocytes and acts as a scavenger receptor for oxidized low-density lipoprotein. Am J Pathol 2009;174:2061-72. [Pubmed]
[88]
Garcia GE, Truong LD, Li P, Zhang P, Johnson RJ, Wilson CB, et al. Inhibition of CXCL16 attenuates inflammatory and progressive phases of anti-glomerular basement membrane antibody-associated glomerulonephritis. Am J Pathol 2007;170:1485-96. [Pubmed]
[89]
Wu T, Xie C, Bhaskarabhatla M, Yan M, Leone A, Chen SS, et al. Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance. Arthritis Rheum 2007;56:949-59. [Pubmed]
[90]
Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390:45-51. [Pubmed]
[91]
Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, et al. Suppression of aging in mice by the hormone Klotho. Science 2005;309:1829-33. [Pubmed]
[92]
Hu MC, Kuro O, Moe OW. The emerging role of Klotho in clinical nephrology. Nephrol Dial Transplant 2012;27:2650-7. [Pubmed]
[93]
Ohnishi M, Razzaque MS. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. FASEB J 2010;24:3562-71. [Pubmed]
[94]
Zhao Y, Banerjee S, Dey N, LeJeune WS, Sarkar PS, Brobey R, et al. Klotho depletion contributes to increased inflammation in kidney of the db/db mouse model of diabetes via RelA (serine)536 phosphorylation. Diabetes 2011;60:1907-16. [Pubmed]
[95]
Aizawa H, Saito Y, Nakamura T, Inoue M, Imanari T, Ohyama Y, et al. Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats. Biochem Biophys Res Commun 1998;249:865-71. [Pubmed]
[96]
Sugiura H, Yoshida T, Tsuchiya K, Mitobe M, Nishimura S, Shirota S, et al. Klotho reduces apoptosis in experimental ischaemic acute renal failure. Nephrol Dial Transplant 2005;20:2636-45. [Pubmed]
[97]
Thurston RD, Larmonier CB, Majewski PM, Ramalingam R, Midura-Kiela M, Laubitz D, et al. Tumor necrosis factor and interferon-gamma down-regulate Klotho in mice with colitis. Gastroenterology 2010;138:1384-94.
[98]
Haruna Y, Kashihara N, Satoh M, Tomita N, Namikoshi T, Sasaki T, et al. Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Natl Acad Sci U S A 2007;104:2331-6. [Pubmed]
[99]
Sugiura H, Yoshida T, Mitobe M, Yoshida S, Shiohira S, Nitta K, et al. Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70. Nephrol Dial Transplant 2010;25:60-8. [Pubmed]
[100]
Hu MC, Shi M, Zhang J, Quinones H, Kuro-o M, Moe OW. Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective. Kidney Int 2010;78:1240-51. [Pubmed]
[101]
Campbell KJ, Rocha S, Perkins ND. Active repression of antiapoptotic gene expression by RelA(p65) NF-kappa B. Mol Cell 2004;13:853-65. [Pubmed]
[102]
Aarenstrup L, Flindt EN, Otkjaer K, Kirkegaard M, Andersen JS, Kristiansen K. HDAC activity is required for p65/RelA-dependent repression of PPARdelta-mediated transactivation in human keratinocytes. J Invest Dermatol 2008;128:1095-106. [Pubmed]
[103]
Liu MY, Khachigian LM. Histone deacetylase-1 is enriched at the platelet-derived growth factor-D promoter in response to interleukin-1beta and forms a cytokine-inducible gene-silencing complex with NF-kappab p65 and interferon regulatory factor-1. J Biol Chem 2009;284:35101-12. [Pubmed]
[104]
Wan F, Lenardo MJ. Specification of DNA binding activity of NF-kappaB proteins. Cold Spring Harb Perspect Biol 2009;1:a000067. [Pubmed]
[105]
Basak S, Hoffmann A. Crosstalk via the NF-kappaB signaling system. Cytokine Growth Factor Rev 2008;19:187-97. [Pubmed]
[107]
Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 2007;8:49-62. [Pubmed]
[108]
Salminen A, Huuskonen J, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging. Ageing Res Rev 2008;7:83-105. [Pubmed]
[109]
109. Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000;908:244-54.
[110]
Chen G, Shaw MH, Kim YG, Nunez G. NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol 2009;4:365-98. [Pubmed]
[111]
Guijarro C, Egido J. Transcription factor-kappa B (NF-kappa B) and renal disease. Kidney Int 2001;59:415-24. [Pubmed]
[112]
Bonizzi G, Bebien M, Otero DC, Johnson-Vroom KE, Cao Y, Vu D, et al. Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers. EMBO J 2004;23:4202-10. [Pubmed]
[113]
Ghosh S, Hayden MS. New regulators of NF-kappaB in inflammation. Nat Rev Immunol 2008;8:837-48. [Pubmed]
[114]
Ortiz-Muñoz G, Lopez-Parra V, Lopez-Franco O, Fernandez-Vizarra P, Mallavia B, Flores C, et al. Suppressors of cytokine signaling abrogate diabetic nephropathy. J Am Soc Nephrol 2010;21:763-72. [Pubmed]
[115]
Hoffmann A, Leung TH, Baltimore D. Genetic analysis of NF-kappaB/Rel transcription factors defines functional specificities. EMBO J 2003;22:5530-9. [Pubmed]
