The Death Ligand TRAIL in Diabetic Nephropathy

Lorz, Corina; Benito-Martín, Alberto; Boucherot, Anissa; Ucero, Álvaro C.; Rastaldi, Maria Pia; Henger, Anna; Armelloni, Silvia; Santamaría, Beatriz; Berthier, Céline C.; Kretzler, Matthias; Egido, Jesús; Ortíz, Alberto

doi:10.1681/asn.2007050581

Cited by 101 publications

(143 citation statements)

References 48 publications

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“…A recent study has observed that osteoprotegerin is strongly upregulated at the RNA level in kidney samples from patients with diabetes [37]. This is interesting in relation to our observation that osteoprotegerin concentration predicts ESRD.…”

Section: Discussionsupporting

confidence: 81%

Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy

et al. 2008

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Aims/hypothesis The bone-related peptide osteoprotegerin is produced by vascular cells and is involved in the process of vascular calcification. The aim of this study was to investigate the predictive value of plasma levels of osteoprotegerin in relation to mortality, cardiovascular events and deterioration in kidney function in patients with type 1 diabetes. Methods This prospective observational follow-up study included 397 type 1 diabetic patients with overt diabetic nephropathy (243 men; age [mean±SD] 42.1±10.6 years, duration of diabetes 28.3±9.9 years, GFR 67±28 ml min −1 1.73 m 2 ) and a group of 176 patients with longstanding type 1 diabetes and persistent normoalbuminuria (105 men; age 42.6±9.7 years, duration of diabetes 27.6±8.3 years).Results The median (range) follow-up period was 11.3 (0.0-12.9) years. Among patients with diabetic nephropathy, individuals with high osteoprotegerin levels (fourth quartile) had significantly higher all-cause mortality than patients with low levels (first quartile) (covariate-adjusted hazard ratio [HR] 3

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Section: Discussionsupporting

confidence: 81%

Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy

et al. 2008

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“…Histology and immunohistochemistry. Following the previously described protocol (19), immunohistochemistry studies were performed from an independent cohort of control subjects (histologically verified unaffected regions from tumor nephrectomies), type 2 progressive diabetic nephropathy case subjects, and other kidney disease biopsies (online appendix Table 3). Jak2 staining was performed using a primary monoclonal antibody at 1:100 (AHO1352; Biosource, Camarillo, CA).…”

Section: Methodsmentioning

confidence: 99%

Enhanced Expression of Janus Kinase–Signal Transducer and Activator of Transcription Pathway Members in Human Diabetic Nephropathy

et al. 2009

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OBJECTIVE— Glomerular mesangial expansion and podocyte loss are important early features of diabetic nephropathy, whereas tubulointerstitial injury and fibrosis are critical for progression of diabetic nephropathy to kidney failure. Therefore, we analyzed the expression of genes in glomeruli and tubulointerstitium in kidney biopsies from diabetic nephropathy patients to identify pathways that may be activated in humans but not in murine models of diabetic nephropathy that fail to progress to glomerulosclerosis, tubulointerstitial fibrosis, and kidney failure. RESEARCH DESIGN AND METHODS— Kidney biopsies were obtained from 74 patients (control subjects, early and progressive type 2 diabetic nephropathy). Glomerular and tubulointerstitial mRNAs were microarrayed, followed by bioinformatics analyses. Gene expression changes were confirmed by real-time RT-PCR and immunohistological staining. Samples from db/db C57BLKS and streptozotocin-induced DBA/2J mice, commonly studied murine models of diabetic nephropathy, were analyzed. RESULTS— In human glomeruli and tubulointerstitial samples, the Janus kinase (Jak)-signal transducer and activator of transcription (Stat) pathway was highly and significantly regulated. Jak-1, -2, and -3 as well as Stat-1 and -3 were expressed at higher levels in patients with diabetic nephropathy than in control subjects. The estimated glomerular filtration rate significantly correlated with tubulointerstitial Jak-1, -2, and -3 and Stat-1 expression ( R 2 = 0.30–0.44). Immunohistochemistry found strong Jak-2 staining in glomerular and tubulointerstitial compartments in diabetic nephropathy compared with control subjects. In contrast, there was little or no increase in expression of Jak/Stat genes in the db/db C57BLKS or diabetic DBA/2J mice. CONCLUSIONS— These data suggest a direct relationship between tubulointerstitial Jak/Stat expression and progression of kidney failure in patients with type 2 diabetic nephropathy and distinguish progressive human diabetic nephropathy from nonprogressive murine diabetic nephropathy.

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“…51 TNF or TNF-related apoptosis-induced ligand activates simultaneous death and NF-B-dependent survival signals in renal cells. 52 Inhibition of NF-B in these circumstances promotes cell death; however, NF-B/RelA activation is involved in the apoptosis of podocytes in HIV-transgenic mice mediated by NF-B-dependent Fas and Fas ligand expression in nephrotoxin and ischemia-induced tubular cell apoptosis. 42,49,53,54 …”

Section: Regulation Of Transcriptionmentioning

confidence: 99%