Paige Charlotte Alison Phillips, Mafalda de Sousa Loreto Aresta Branco, Chelsy Louise Cliff, Joanna Kate Ward, Paul Edward Squires, Claire Elizabeth Hills
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引用次数: 0
Abstract
Background/aims: As a microvascular complication, diabetic kidney disease is the leading cause of chronic kidney disease and end-stage renal disease worldwide. While the underlying pathophysiology driving transition of diabetic kidney disease to renal failure is yet to be fully understood, recent studies suggest that cellular senescence is central in disease development and progression. Consequently, understanding the molecular mechanisms which initiate and drive senescence in response to the diabetic milieu is crucial in developing targeted therapies that halt progression of renal disease.
Methods: To understand the mechanistic pathways underpinning cellular senescence in the context of diabetic kidney disease, we reviewed the literature using PubMed for English language articles that contained key words related to senescence, inflammation, fibrosis, senescence-associated secretory phenotype (SASP), autophagy, and diabetes.
Results: Aberrant accumulation of metabolically active senescent cells is a notable event in the progression of diabetic kidney disease. Through autocrine- and paracrine-mediated mechanisms, resident senescent cells potentiate inflammation and fibrosis through increased expression and secretion of pro-inflammatory cytokines, chemoattractants, recruitment of immune cells, myofibroblast activation, and extracellular matrix remodelling. Compounds that eliminate senescent cells and/or target the SASP - including senolytic and senomorphics drugs - demonstrate promising results in reducing the senescent cell burden and associated pro-inflammatory effect.
Conclusions: Here we evidence the link between senescence and diabetic kidney disease and highlight underlying molecular mechanisms and potential therapeutic targets that could be exploited to delay disease progression and improve outcomes for individuals with the disease. Trials are now required to translate their therapeutic potential to a clinical setting.
期刊介绍:
Diabetic Medicine, the official journal of Diabetes UK, is published monthly simultaneously, in print and online editions.
The journal publishes a range of key information on all clinical aspects of diabetes mellitus, ranging from human genetic studies through clinical physiology and trials to diabetes epidemiology. We do not publish original animal or cell culture studies unless they are part of a study of clinical diabetes involving humans. Categories of publication include research articles, reviews, editorials, commentaries, and correspondence. All material is peer-reviewed.
We aim to disseminate knowledge about diabetes research with the goal of improving the management of people with diabetes. The journal therefore seeks to provide a forum for the exchange of ideas between clinicians and researchers worldwide. Topics covered are of importance to all healthcare professionals working with people with diabetes, whether in primary care or specialist services.
Surplus generated from the sale of Diabetic Medicine is used by Diabetes UK to know diabetes better and fight diabetes more effectively on behalf of all people affected by and at risk of diabetes as well as their families and carers.”