The emerging role of the apelinergic system in kidney physiology and disease

Abstract

The apelinergic system (AS) is a novel pleiotropic system with an essential role in renal and cardiovascular physiology and disease, including water homeostasis and blood pressure regulation. It consists of two highly conserved peptide ligands, apelin and apela, and a G-protein-coupled apelin receptor. The two ligands have many isoforms and a short half-life, and exert both similar and divergent effects. Vasopressin, apelin and their receptors colocalize in hypothalamic regions essential for body fluid homeostasis and interact at the central and renal levels to regulate water homeostasis and diuresis in inverse directions. In addition, the AS and renin angiotensin system interact both systemically and in the kidney, with implications for the cardiovascular system. A role for the AS in diverse pathological states, including disorders of sodium and water balance, hypertension, heart failure, pre-eclampsia, acute kidney injury, sepsis and diabetic nephropathy has recently been reported. Furthermore, several metabolically stable apelin analogs have been developed, with potential applications in diverse diseases. We review here what is currently known about the physiological functions of the AS, focusing on renal, cardiovascular and metabolic homeostasis, and the role of the AS in associated diseases. We also describe several hurdles and research opportunities worthy of the attention of the nephrology community.

Apelin-13 Decreases Epithelial Sodium Channel (ENaC) Expression and Activity in Kidney Collecting Duct Cells

“…4, treatment with apelin-13 induced significant ERK phosphorylation after 30 min whereas this phosphorylation could not be maintained until 60 min (n=5). These results suggest that the ERK pathway is involved in the apelin regulation of ENaC, in accordance with the mechanisms previously described in the action of the apelinergic system in the kidney [40,41].…”

The Apelinergic System: Apelin, ELABELA, and APJ Action on Cell Apoptosis: Anti-Apoptotic or Pro-Apoptotic Effect?

“…Depending on the type of cells and doses used, apelin shows different effects, which is the basis for the contradictory data in the literature. Nevertheless, apelin mainly shows anti-apoptotic activity, which is an introduction to research and a potential therapeutic target for various cancers [3,4] but also for many dysfunctions and diseases of the neurological, cardiovascular, and urinary systems (Figure 4). A second ligand for the APJ receptor was recently discovered, which also regulates cell apoptosis.…”

“…Disruption of cell apoptosis has been linked to a variety of disorders, such as autoimmune and neurodegenerative diseases, diabetes, and cancer [2]. Certain authors report on the expression and role of the apelinergic system in the progression of various types of cancer such as breast [3] and kidney [4], suggesting therapeutic potential in the future [5,6]. Several factors such as hormones and neuropeptides can regulate cell apoptosis.…”

The Role of Apelin–APJ System in Diabetes and Obesity

“…It was increased in some research ( 67 , 68 ), while it was decreased in other research ( 69 ). It is speculated that a lower apelin level may be caused by apelin-regulated insulin sensitivity, which stimulates glucose utilization and enhances brown adipogenesis ( 70 ). In high-glucose-medium-cultured podocytes, APJ mRNA is upregulated when compared to the normal condition ( 71 ).…”