Review
Version 1
Preserved in Portico This version is not peer-reviewed
Protein-Bound Uremic Toxins in Senescence and Kidney Fibrosis
Version 1
: Received: 8 August 2023 / Approved: 9 August 2023 / Online: 9 August 2023 (10:49:19 CEST)
A peer-reviewed article of this Preprint also exists.
Yang, Y.; Mihajlovic, M.; Masereeuw, R. Protein-Bound Uremic Toxins in Senescence and Kidney Fibrosis. Biomedicines 2023, 11, 2408. Yang, Y.; Mihajlovic, M.; Masereeuw, R. Protein-Bound Uremic Toxins in Senescence and Kidney Fibrosis. Biomedicines 2023, 11, 2408.
Abstract
Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Recent studies provide some clues that PBUTs may also promote senescence in kidney tubular cells. This review provides an overview on how senescence contributes to CKD and the involvement of PBUTs in this process, and how kidney senescence can be studied, Finally, some suggestions for future therapeutic options for CKD while targeting senescence are given.
Keywords
chronic kidney disease; uremic toxins; renal tubular transport; extracellular matrix remodeling; apoptosis resistance; inflammatory response; senescence-associated secretory phenotype factors
Subject
Medicine and Pharmacology, Urology and Nephrology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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