Cellular Basis of Diabetic Nephropathy

Abstract

Transforming growth factor-␤ (TGF-␤) may be critical in the development of diabetic nephropathy (DN), and genetic predisposition is an important determinant of DN risk. We evaluated mRNA expression levels of TGF-␤ system components in cultured skin fibroblasts (SFs) from type 1 diabetic patients with fast versus slow development of DN. A total of 125 long-standing type 1 diabetic patients were ranked by renal mesangial expansion score (MES) based on renal biopsy findings and diabetes duration. Patients in the highest quintile of MES who were also microalbuminuric or proteinuric (n ‫؍‬ 16) were classified as "fast-track" for DN, while those in the lowest quintile who were also normoalbuminuric (n ‫؍‬ 23) were classsified as "slow-track" for DN. Twenty-five normal subjects served as control subjects. SFs were cultured in medium with 25 mmol/l glucose for 36 h. SF mRNA expression levels for TGF-␤1, TGF-␤ type II receptor (TGF-␤ RII), thrombospondin-1, and latent TGF-␤ binding protein-1 (LTBP-1) were measured by real-time RT-PCR. LTBP-1 mRNA expression was reduced in slow-track (0.99 ؎ 0.38) versus fast-track patients (1.65 ؎ 0.52, P ‫؍‬ 0.001) and control subjects (1.41 ؎ 0.7, P ‫؍‬ 0.025). mRNA levels for TGF-␤1, TGF-␤ RII, and thrombospondin-1 were similar in the three groups. Reduced LTBP-1 mRNA expression in SFs from slow-track patients may reflect genetically determined DN protection and suggests that LTBP-1 may be involved in the pathogenesis of DN through the regulation of TGF-␤ activity.

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

“…We also demonstrated that the upregulation of Tgfb expression and protein levels in diabetic kidneys were markedly inhibited in BNP-Tg mice (Figs 3, 4). Considering a pathogenic role for TGF-β in cellular dysfunction, fibrogenesis and glomerular hypertrophy in diabetes [3,28,35], it is conceivable that the inhibition of renal TGF-β system activation contributed significantly to the observed protective effects of BNP from diabetic renal injury. Although the effect of BNP on glomerular haemodynamics was not investigated, it may be possible that the chronic excess of BNP lessened glomerular hypertension by inhibiting the RAS and TGF-β system tonically.…”

Epithelial-to-Mesenchymal Transition in Early Transplant Tubulointerstitial Damage

“…The primers for the EMT-and MET-associated genes (Table 5) were designed using Oligo6 (Molecular Biology Insights, Cascade, CO) or PRIMER3 32 or obtained from peer-reviewed articles. 33,34 For primer design, the mRNA gene sequences were obtained from GenBank, 35,36 and exact full-sequence alignment was validated by BLASTN. 37 QRT-PCR was performed on all samples used on the arrays, including those that were inadequate for the arrays (n ϭ 55), using SYBR Green I detection system with heat-activated Taq DNA polymerase and uracil DNA glycosylase (Platinum SYBR Green qPCR SuperMix-UDG; Invitrogen).…”

Diabetes Mellitus: Role of Free Radicals and Oxidative Stress

“…[16] Symptoms Blurred vision, polyurea, polyphagia, polydipsia, weight loss, constipation, cramps, thirst, hunger, weakness, [17,18] and candidiasis are common symptoms for both type-1 and type-2 DM. [1] Apart from that the patients with Type-1 DM have both microvascular problems [5][6][7][8][9][10] and macrovascular diseases such as heart, peripheral vascular and coronary artery diseases [11,12] while patients with Type 2 DM have high risk of large vessel atherosclerosis commonly associated with obesity, hypertension, hyperlipidaemia. [11,12,19,20] Most patients are die with type-2 diabetes due to cardiovascular complications and end stage renal disorder.…”

“…Deficiency of insulin leads to chronic hyperglycemia with disturbances of fat, protein and carbohydrate metabolism. [1][2][3][4] Long term diabetes cause tissue or vascular damage and leads some dangerous complications like neuropathy [5,6] , nephropathy [7,8] , retinopathy [9,10] , cardiovascular complications [11,12] and ulceration. [13,14] First diabetic classification and diagnostic criteria was given by World Health…”