Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy.

  title={Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy.},
  author={Daniela Verzola and Maria Teresa Gandolfo and G D Gaetani and Anna Maria Ferraris and Rosa Mangerini and Franco Ferrario and Barbara Villaggio and Fabio Gianiorio and Francesca Tosetti and Ursula Keller Weiss and Paolo Traverso and Mariano Mji and Giacomo Deferrari and Giacomo Garibotto},
  journal={American journal of physiology. Renal physiology},
  volume={295 5},
We examined the hypothesis that senescence represents a proximate mechanism by which the kidney is damaged in type 2 diabetic nephropathy (DN). As a first step, we studied whether the senescence-associated beta-galactosidase (SA-beta-Gal) and the cell cycle inhibitor p16INK4A are induced in renal biopsies from patients with type 2 DN. SA-beta-Gal staining was approximately threefold higher (P < 0.05) than in controls in the tubular compartment of diabetic kidneys and correlated directly with… 

Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy.

Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis

  • Chen YangJing Xue Hua-feng Liu
  • Medicine, Biology
    Medical science monitor : international medical journal of experimental and clinical research
  • 2018
Background The aim of this study was to determine whether senescence in renal glomeruli is involved in lupus nephritis (LN); the expression of senescence-associated β-galactosidase (SA-β-Gal) and its

Accelerated senescence of renal tubular epithelial cells is associated with disease progression of patients with immunoglobulin A (IgA) nephropathy.

Metformin Improves the Senescence of Renal Tubular Epithelial Cells in a High-Glucose State Through E2F1

It is shown that metformin alleviates high-glucose-induced senescence and fibrosis of renal tubular epithelial cells by downregulating the expression of E2F1.

Role of Senescent Renal Cells in Pathophysiology of Diabetic Kidney Disease

Current literature linking senescence to DKD is reviewed and the likely routes to intervention in a clinical setting are speculated, with senescent cells an appealing target for intervention in these disorders.

Transition of kidney tubule cells to a senescent phenotype in early experimental diabetes.

It is shown that kidney proximal tubule cells in culture transition to senescence in response to oxidative stress, delineating a phenotypic change in cortical tubules early in the pathogenesis of diabetes that may contribute to further downstream complications of the disease.

Albumin-induced premature senescence in human renal proximal tubular cells and its relationship with intercellular fibrosis

BSA induces renal tubular epithelial cell premature senescence, which regulates the G2/M phase through the CDC25C/CDK1 pathway, leading to tubulointerstitial fibrosis.

Senescence marker activin A is increased in human diabetic kidney disease: association with kidney function and potential implications for therapy

Circulating activin A is increased in human DKD and correlates with reduced kidney function and kidney injury markers, which underscore the role of inflammation and provide a basis for further exploration ofactivin A as a diagnostic marker and therapeutic target in DKD.

Upregulation of MiR-126 Delays the Senescence of Human Glomerular Mesangial Cells Induced by High Glucose via Telomere-p53-p21-Rb Signaling Pathway

It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs and may serve as a new strategy for the treatment of DKD.



Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes.

Changes in podocyte structure and density occur since the early stages of diabetic nephropathy and might contribute to increasing albuminuria in type 2 diabetic patients.

Premature senescence of skin fibroblasts from insulin-dependent diabetic patients with kidney disease.

It is concluded that an acceleration of cell aging is a peculiar feature of diabetic kidney disease and may contribute to its pathological tissue changes.

Apoptosis in the kidneys of patients with type II diabetic nephropathy.

The findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.

Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in kidneys with glomerular disease.

K kidneys with GD display increased expression of senescence marker p16(INK4A) in glomerular and interstitial cell nuclei compared to kidneys with normal aging or TIN, and the findings suggest a role for somatic cellsenescence mechanisms in progression of GD.

Tubular cell senescence and expression of TGF-beta1 and p21(WAF1/CIP1) in tubulointerstitial fibrosis of aging rats.

The data suggest that tubular cells undergo senescence and express increased TGF-beta1 and p21WAF1/CIP1 with advancing age, which may play an important role in the initiation and/or progression of tubulointerstitial fibrosis and glomerulosclerosis in aging.

The cyclin kinase inhibitor p21WAF1/CIP1 is required for glomerular hypertrophy in experimental diabetic nephropathy.

Evidence is provided that the cyclin kinase inhibitor p21 may be required for diabetic glomerular hypertrophy induced by TGF-beta1, and the absence ofglomerularhypertrophy appears protective of renal function in diabetic mice.

Testosterone promotes apoptotic damage in human renal tubular cells.

Results indicate that T increases the permissiveness of proximal tubule kidney cells to apoptotic effects by triggering an apoptotic pathway involving caspase activation, Fas up-regulation, and FasL expression, thus potentially interacting with mechanisms of cell loss which have been already shown to be activated in chronic renal diseases.

Telomere shortening in kidneys with age.

It is indicated that telomeres shorten in an age-dependent manner in the kidney, either due to developmental factors or aging, particularly in renal cortex.

The podocyte and diabetes mellitus: is the podocyte the key to the origins of diabetic nephropathy?

Understanding the cellular and molecular basis for changes in podocyte structure and function in diabetes mellitus may lead to novel diagnostic tools and treatment strategies for diabetic nephropathy.

Taurine Prevents Apoptosis Induced by High Ambient Glucose in Human Tubule Renal Cells

It is demonstrated that taurine attenuates hyperglycemia-induced apoptosis in human tubular cells via an inhibition of oxidative stress and could exert a beneficial effect in preventing tubulointerstitial injury in diabetic nephropathy.