Acetylation in renal physiology and pathophysiology

The kidney, one of the most important organs in the human body, is vital for maintaining overall health and homeostasis. However, kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), have become serious global public health issues. Post-translational modification (PTM) of proteins, especially acetylation, can affect the pathophysiology of the kidney through various pathways, including the regulation of inflammatory responses, fibrosis, apoptosis, and autophagy. Acetylation is primarily regulated by two enzymes: histone acetyltransferases (HATs) and histone deacetylases (HDACs). There are 11 known HDAC isoforms that influence the onset and progression of kidney disease by affecting the acetylation level of key proteins. Additionally, sirtuins (SIRTs), which belonging to class III HDACs, regulate multiple biological processes to exert protective effects on the kidneys and delay the progression of kidney diseases. Intriguingly, some SIRTs exhibit dual roles (protective/detrimental) in various renal disease models. Many HDAC inhibitors and SIRT activators have been widely used in the clinical treatment of various kidney diseases. In this review, we summarize the roles and mechanisms of HDACs and SIRTs in kidney diseases and then review the potential therapeutic effects of some SIRT activators and HDAC inhibitors in kidney protection. Notably, we also discuss the mechanism of SIRTs with dual roles in kidney protection and injury and introduce some agonists and inhibitors targeting these SIRTs.