Altered Chaperone and Protein Turnover Regulators Expression in Cultured Skin Fibroblasts from Type 1 Diabetes Mellitus with Nephropathy

Tessari, Paolo; Puricelli, Lucia; Iori, Elisabetta; Arrigoni, Giorgio; Vedovato, Monica; James, Peter; Coracina, and Anna; Millioni, Renato

doi:10.1021/pr060443n

Cited by 24 publications

(20 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SNPs within HSP70-2 and HSP70-hom have been first characterized by Milner and Campbell [17]. Few studies highlighting the important role of HSP-70 in T1DM with DN [29], T2DM [30] and cardiovascular events in T2DM patients [31]. In the present study, all 946 subjects were genotyped for HSP70-2 and HSP70-hom SNPs in different stages of DN subjects.…”

Section: Discussionmentioning

confidence: 97%

Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population

et al. 2017

View full text Add to dashboard Cite

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease, characterized by progressive albuminuria and conferring additional risk of cardiovascular disease (CVD) and mortality. The crucial role of heat-shock proteins (HSPs) on renal function in patients with DN has been well documented. The present study was aimed to understand the association of HSP-70 gene variants on the susceptibility of Type 2 Diabetes Mellitus (T2DM) and DN. A total of 946 subjects (549 Males; 397 Females) were recruited and divided into four groups according to the levels of urinary albumin excretion (UAE): those with normoalbuminuria (UAE <30 mg/24 h; n=230), those with microalbuminuria (30≤ UAE ≤300 mg/24 h; n=230), and those with macroalbuminuria (UAE> 300 mg/24 h; n=230). The control group randomly enrolled a consecutive population of 256 healthy subjects who had a routine medical check-up in our hospital. Those subjects had no history or clinical symptoms of diabetes. Subjects were genotyped for HSP70-2 (+1538 A/G; rs2763979) and HSP70-hom (+2437 C/T; rs2227956) by PCR-restriction fragment length polymorphism (RFLP). The ‘G’ allele of HSP70-2 (+1538 A/G) single nucleotide polymorphism (SNP) showed relative risk for normoalbuminuria, microalbuminuria and macroalbuminuria subjects whereas the ‘T’ allele of HSP70-hom (+2437 C/T) SNP showed significant protection against macroalbuminuria subjects. In conclusion, our results indicate that the HSP70-2 (+1538 A/G) and HSP70-hom (+2437 C/T) SNPs are highly associated with renal complications in T2DM among the South Indian population.

show abstract

Section: Discussionmentioning

confidence: 97%

Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In addition, TCTP is induced by growth signals, numerous cytokines and various stress conditions, including oxidative stress, heat shock and endoplasmic reticulum stress [25]. A recent proteomic analysis of cultured skin fibroblasts showed an upregulation of TCTP in patients with DN [26]. As cultured skin fibroblasts are a suitable cell model for investigating the mechanisms of DN development [27], the production pattern of TCTP was assumed to be similar in renal cells under diabetic conditions.…”

Section: Discussionmentioning

confidence: 99%

Translationally controlled tumour protein is associated with podocyte hypertrophy in a mouse model of type 1 diabetes

Kim

Nam

et al. 2012

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Translationally controlled tumour protein (TCTP) is thought to be involved in cell growth by regulating mTOR complex 1 (mTORC1) signalling. As diabetes characteristically induces podocyte hypertrophy and mTORC1 has been implicated in this process, TCTP may have a role in the pathogenesis of diabetes-induced podocyte hypertrophy. Methods We investigated the effects and molecular mechanisms of TCTP in diabetic mice and in high glucose-stimulated cultured podocytes. To characterise the role of TCTP, we conducted lentivirus-mediated gene silencing of TCTP both in vivo and in vitro. Results Glomerular production of TCTP was significantly higher in streptozotocin induced-diabetic DBA/2J mice than in control animals. Double-immunofluorescence staining for TCTP and synaptopodin revealed that podocyte was the principal cell responsible for this increase. TCTP knockdown attenuated the activation of mTORC1 downstream effectors and the overproduction of cyclin-dependent kinase inhibitors (CKIs) in diabetic glomeruli, along with a reduction in proteinuria and a decrease in the sizes of podocytes as well as glomeruli. In addition, knockdown of TCTP in db/db mice prevented the development of diabetic nephropathy, as indicated by the amelioration of proteinuria, mesangial expansion, podocytopenia and glomerulosclerosis. In accordance with the in vivo data, TCTP inhibition abrogated high glucose-induced hypertrophy in cultured podocytes, which was accompanied by the downregulation of mTORC1 effectors and CKIs. Conclusions/interpretation These findings suggest that TCTP might play an important role in the process of podocyte hypertrophy under diabetic conditions via the regulation of mTORC1 activity and the induction of cell-cycle arrest.

show abstract

“…3) participate in various metabolic pathways including glycolysis (phosphoglycerate mutase and gamma-enolase), the citric acid cycle (dihydrolipoyl dehydrogenase), lipid metabolism (sterol carrier protein x) and ketolysis (succinyl CoA: 3-ketoacid-coenzyme A transferase 1). In other tissues prone to diabetic complications, such as liver, kidney and both skeletal and heart muscle, energy metabolism is one of the key areas affected [28][29][30][31][32]. However, metabolic changes associated with diabetes are tissue-specific.…”

Section: Resultsmentioning

confidence: 99%

Human retinal pigment epithelium proteome changes in early diabetes

et al. 2008

View full text Add to dashboard Cite

Aims/hypothesis Diabetic retinopathy is the most common complication of diabetes and a leading cause of blindness among working-age adults. Anatomical and functional changes occur in the retina and retinal pigment epithelium (RPE) prior to clinical symptoms of the disease. However, the molecular mechanisms responsible for these early changes, particularly in the RPE, remain unclear. To begin defining the molecular changes associated with pre-retinopathic diabetes, we conducted a comparative proteomics study of human donor RPE. Methods The RPE was dissected from diabetic human donor eyes with no clinically apparent diabetic retinopathy (n=6) and from eyes of age-matched control donors (n= 17). Soluble proteins were separated based upon their mass and charge using two-dimensional (2-D) gel electrophoresis. Protein spots were visualised with a fluorescent dye and spot densities were compared between diabetic and control gels. Proteins from spots with significant disease-related changes in density were identified using mass spectrometry.Results Analysis of 325 spots on 2-D gels identified 31 spots that were either up-or downregulated relative to those from age-matched control donors. The protein identity of 18 spots was determined by mass spectrometry. A majority of altered proteins belonged to two major functional groups, metabolism and chaperones, while other affected categories included protein degradation, synthesis and transport, oxidoreductases, cytoskeletal structure and retinoid metabolism. Conclusions/interpretation Changes identified in the RPE proteome of pre-retinopathic diabetic donor eyes compared with age-matched controls suggest specific cellular alterations that may contribute to diabetic retinopathy. Defining the pre-retinopathic changes affecting the RPE could provide important insight into the molecular events that lead to this disease.

show abstract

Altered Chaperone and Protein Turnover Regulators Expression in Cultured Skin Fibroblasts from Type 1 Diabetes Mellitus with Nephropathy

Cited by 24 publications

References 68 publications

Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population

Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population

Translationally controlled tumour protein is associated with podocyte hypertrophy in a mouse model of type 1 diabetes

Human retinal pigment epithelium proteome changes in early diabetes

Contact Info

Product

Resources

About