Endoplasmic Reticulum stress in chronic kidney disease. New molecular targets from bench to the bedside

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Carlo Alberto Ricciardi, Luigi Gnudi

King’s College of London, Faculty of Life Sciences & Medicine, School of Cardiovascular Medicine & Sciences, Section Vascular Biology and Inflammation, British Heart Foundation Centre for Research Excellence.

Corrispondenza a:
Carlo Alberto Ricciardi
School of Cardiovascular Medicine & Sciences, Section Vascular Biology and Inflammation, Unit for Metabolic Medicine
King’s College London, Franklin Wilkins Building
Stamford street
SE1 9NH London
United Kingdom
Tel: +44(0)2078484464
Email: carlo.1.ricciardi@kcl.ac.uk

 

Abstract

The identification of new biomarkers/pharmacological targets for chronic kidney disease (CKD) is required for the development of more effective therapies. Several studies in vitro and in vivo have shown the importance of the endoplasmic reticulum (ER) (cellular organelle devolved to protein biosynthesis and maturation, and cellular detoxification processes) in the pathophysiology of CKD.

Hence, the synthesis and development of novel drugs against the different ER intracellular pathways is crucial in order to slow down the development and progression of renal diseases.

This review aims to dissect the role of the different ER branches (PERK, IRE1α, ATF6) and their function in CKD, providing potential insights for the development of new treatments.

Keywords: endoplasmic reticulum, chronic kidney disease, unfolded protein response, reticulon

 

Endoplasmic reticulum

The endoplasmic reticulum (ER) is a continuum of tubules and vesicles morphologically divided in “rough” ER (containing ribosomes attached on the cytosolic border that serves as the site of biological protein synthesis)[1] and “smooth” ER, lacking ribosomes.

Lack or presence of ribosome reflects the multi-functional nature of the ER. In eukaryotic cells, the rough ER has a pivotal function in protein biosynthesis serving as point for the secretory pathway and in the folding and maturation of protein within the cell [2], while the smooth ER is involved in carbohydrates metabolism, drugs detoxification and calcium storage [3].

Protein folding is required to create a functional protein able to exert its function; the ER is a cellular organelle that rectifies abnormal protein folding/function by acting on protein that need to be physiologically replaced/restored or have been damaged by external insults; this process is defined as “unfolded protein response” (UPR). ER could be considered as a signalling platform that responds to stimuli from in and outside the cells with the aim of maintaining cellular functions.

 

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