Expression pattern of genes in peripheral blood mononuclear cells in diabetic nephropathy

Moczulski, Dariusz; Fojcik, H.; Wielgorecki, A.; Trautsolt, Wanda; B, Gawlik; Kosiorz-Gorczynska, S.; Oczko-Wojciechowska, Małgorzata; Wiench, Małgorzata; Strojek, K; Żukowska-Szczechowska, E; Grzeszczak, W

doi:10.1111/j.1464-5491.2006.02067.x

Cited by 12 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent study, peripheral mononuclear blood cells from diabetic patients with and without diabetic nephropathy were screened/compared for candidate target genes using microarray technology. TSP-1 was one out of four differentially regulated genes, suggesting that TSP-1 expression is important for the pathogenesis of diabetic nephropathy in humans (43). In addition, the fact that we could show similar results regarding TSP-1-mediated TGF-␤ activation and matrix accumulation using mice of two different backgrounds strongly supports the relevance of these findings.…”

Section: Tsp-1 Activates Tgf-␤ In Diabetic Nephropathysupporting

confidence: 74%

Thrombospondin-1 Is an Endogenous Activator of TGF-β in Experimental Diabetic Nephropathy In Vivo

et al. 2007

View full text Add to dashboard Cite

OBJECTIVE—Transforming growth factor-β (TGF-β), the central cytokine responsible for the development of diabetic nephropathy, is usually secreted as a latent procytokine complex that has to be activated before it can bind to its receptors. Recent studies by our group demonstrated that thrombospondin-1 (TSP-1) is the major activator of latent TGF-β in experimental glomerulonephritis in the rat, but its role in diabetic nephropathy in vivo is unknown. RESEARCH DESIGN AND METHODS—Type 1 diabetes was induced in wild-type (n = 27) and TSP-1–deficient mice (n = 36) via streptozotocin injection, and diabetic nephropathy was investigated after 7, 9.5, and 20 weeks. Renal histology, TGF-β activation, matrix accumulation, and inflammation were assessed by immunohistology. Expression of fibronectin and TGF-β was evaluated using real-time PCR. Furthermore, functional parameters were examined. RESULTS—In TSP-1–deficient compared with wild-type mice, the amount of active TGF-β within glomeruli was significantly lower, as indicated by staining with specific antibodies against active TGF-β or the TGF-β signaling molecule phospho-smad2/3 or the typical TGF-β target gene product plasminogen activator inhibitor-1. In contrast, the amount of glomerular total TGF-β remained unchanged. The development of diabetic nephropathy was attenuated in TSP-1–deficient mice as demonstrated by a significant reduction of glomerulosclerosis, glomerular matrix accumulation, podocyte injury, renal infiltration with inflammatory cells, and renal functional parameters. CONCLUSIONS—We conclude that TSP-1 is an important activator of TGF-β in diabetic nephropathy in vivo. TSP-1–blocking therapies may be considered a promising future treatment option for diabetic nephropathy.

show abstract

Section: Tsp-1 Activates Tgf-␤ In Diabetic Nephropathysupporting

confidence: 74%

Thrombospondin-1 Is an Endogenous Activator of TGF-β in Experimental Diabetic Nephropathy In Vivo

et al. 2007

View full text Add to dashboard Cite

show abstract

“…It catalyzes conversion of composed homocysteine into methionine by remethylation [9]. Polymorphisms which occur on the gene coding MTHFR enzyme lead to hyperhomocysteinemia by reducing enzyme activity [10,11]. Up to now, many polymorphisms on the gene coding MTHFR has been detected, but most of them have not led to hyperhomocysteinemia since they do not alter the shape and activity of active site of the MTHFR enzyme.…”

Section: Introductionmentioning

confidence: 99%

Methyltetrahydrofolate reductase C677T gene mutation and hyperhomocysteinemia as a novel risk factor for diabetic nephropathy

Ükinç

Ersöz

Karahan

et al. 2009

Endocr

View full text Add to dashboard Cite

Hyperhomocysteinemia is a well-defined risk factor for endothelial dysfunction and atherosclerosis. A point mutation (677 C-T) of MTHFR gene results in a significant increase at plasma homocysteine levels. In this study we aimed to evaluate the effects of MTHFR gene mutation and consequent hyperhomocysteinemia on the development of diabetic microvascular complications in comparison with the other defined risk factors. Diabetic patients without a history of macrovascular complication or overt nephropathy enrolled into the study. The presence of MTHFR 677 C-T point mutation was evaluated by Real-Time PCR technique by using a LightCycler. MTHFR heterozygous mutation was present in 24 patients over 52. Patients with diabetes were divided into two groups according to the presence of MTHFR gene mutation. Both groups were well matched regarding age and diabetes duration. Metabolic parameters, plasma homocysteine, microalbuminuria, folic acid, and vitamin B12 levels were also studied. Presence of neuropathy and retinopathy were evaluated by specific tests. Duration of diabetes, BMI, systolic and diastolic blood pressure, plasma CRP, HbA1c, and lipid levels were not different between the two groups. Plasma homocysteine (12.89 +/- 1.74 and 8.98 +/- 1.91 micromol/l; P < 0.0001) and microalbuminuria levels (73.40 +/- 98.15 and 29.53 +/- 5.08 mg/day; P = 0.021) were significantly higher in the group with MTHFR gene mutation while creatinine clearance levels (101.1 +/- 42.6 and 136.21 +/- 51.50 ml/min; P = 0.008) were significantly lower. Sixteen over 22 (73%) of the patients with diabetic nephropathy had MTHFR gene mutation, while this was only 27% (8 over 30) in normoalbuminuric patients (P = 0.017). There was a significant correlation of plasma homocysteine level with microalbuminuria (r = 0.54; P = 0.031) in the patients with diabetic nephropathy who had C677T polymorphism. We did not find any specific association of MTHFR gene mutation and hyperhomocysteinemia with retinopathy or neuropathy.

show abstract

“…Gene expression profiles of peripheral blood mononuclear cells (PBMCs) from diabetic patients with and without DN (with proteinuria or with normoalbuminuria - both with at least 20 years of diabetes duration) focused on 198 candidate genes for diabetic nephropathy (Pubmed search based on gene variants or gene expression analyses) and revealed only thrombospondin 1 (THBS1) and cyclooxygenase 1 (COX1) to be overexpressed in DN PBMCs and matrix metalloproteinase 9 (MMP9) and cyclooxygenase 2 (COX2 genes) repressed in DN PBMCs (39). These differentially regulated molecules have been associated with DN in various model systems, but might also be a consequence of renal disease or proteinuria in general.…”

Section: Introductionmentioning

confidence: 99%

Defining human diabetic nephropathy on the molecular level: Integration of transcriptomic profiles with biological knowledge

Martini

Eichinger

Nair

et al. 2008

Rev Endocr Metab Disord

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is the most common cause for end stage renal disease (ESRD). Next to environmental factors, genetic predispositions determine the susceptibility for DN and its rate of progression to ESRD. With the availability of genome wide expression profiling we have the opportunity to define relevant pathways activated in the individual diabetic patient, integrating both environmental exposure and genetic background. In this review we summarize current understanding of how to link comprehensive gene expression data sets with biomedical knowledge and present strategies to build a transcriptional network of DN. Information about the individual disease processes of DN might allow the implementation of a personalized molecular medicine approach with mechanism-based patient management. Web based search engines like Nephromine are essential tools to facilitate access to molecular data of genomics, proteomics and metabolomics of DN.

show abstract

Expression pattern of genes in peripheral blood mononuclear cells in diabetic nephropathy

Abstract: The different gene expression pattern in peripheral blood mononuclear cells in patients with diabetic nephropathy might indicate an important pathway in the pathogenesis of this complication.

Cited by 12 publications

References 36 publications

Thrombospondin-1 Is an Endogenous Activator of TGF-β in Experimental Diabetic Nephropathy In Vivo

Thrombospondin-1 Is an Endogenous Activator of TGF-β in Experimental Diabetic Nephropathy In Vivo

Methyltetrahydrofolate reductase C677T gene mutation and hyperhomocysteinemia as a novel risk factor for diabetic nephropathy

Defining human diabetic nephropathy on the molecular level: Integration of transcriptomic profiles with biological knowledge

Contact Info

Product

Resources

About