Role of Senescent Renal Cells in Pathophysiology of Diabetic Kidney Disease
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MICROVASCULAR COMPLICATIONS—NEPHROPATHY (B ROSHANRAVAN, SECTION EDITOR)
Role of Senescent Renal Cells in Pathophysiology of Diabetic Kidney Disease Christopher D. Wiley 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Diabetic kidney disease (DKD) is the leading cause of kidney failure in the USA, representing ~ 44% of all cases of kidney failure. Advancements in both glucose management and inhibitors of the renin-angiotensin system have significantly improved prognosis for individuals with DKD, yet DKD continues to affect 30–40% of people with type 2 diabetes and is still a major predictor of mortality in this population. Thus, new interventions are required to address this significant health burden. Recent Findings One potential target for intervention is cellular senescence. Senescence permanently arrests cell division in response to genotoxic, oncogenic, or metabolic stresses—coupled to the secretion of inflammatory cytokines, chemokines, growth factors, proteases, and other molecules that can have potent local and systemic effects. This senescence-associated secretory phenotype (SASP) explains how a relatively small number of senescent cells can promote pathology, and a growing number of degenerative conditions have been found to be caused or aggravated by senescent cells. Many SASP factors are also associated with loss of kidney function. Targeted elimination of senescent cells prevents the development of several degenerative pathologies. Since senescent cells appear in the proximal tubules and podocytes of patients with DKD, they are an appealing target for intervention in these disorders. Summary Here, we review the current literature linking senescence to DKD and speculate on the likely routes to intervention in a clinical setting. Keywords Senescence . Diabetic kidney disease . SASP . Senolytic . Intervention
Introduction Diabetic kidney disease (DKD) is the leading cause of kidney failure in the USA [1–3]. Despite improvements in both glucose and blood pressure regulation, the incidence of DKD and DKD-related mortality remain very high [4–9]. As the percentage of Americans with diabetes grows, identification of new players in the development and progression of DKD is necessary to attenuate the rising tide of kidney disease that accompanies this disorder. This article is part of the Topical Collection on Microvascular Complications—Nephropathy * Christopher D. Wiley [email protected] 1
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA
One potential target for intervention in the development of DKD is cellular senescence. Senescence is a process by which cells respond the endogenous or exogenous stressors by adopting an essentially permanent cell cycle arrest, mediated by cyclin-dependent kinase inhibitors such as p21WAF1, p16INK4a, or p15INK4b [10, 11]. This arrest is coupled to the secretion of a combination of cytokines, chemokines, growth factors, protease, and other molecules collectively known as the senescence
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