The endoplasmic reticulum stress and the unfolded protein response in kidney disease: Implications for vascular growth factors

Abstract

Acute kidney injury (AKI) and chronic kidney disease (CKD) represent an important challenge for healthcare providers. The identification of new biomarkers/pharmacological targets for kidney disease is required for the development of more effective therapies. Several studies have shown the importance of the endoplasmic reticulum (ER) stress in the pathophysiology of AKI and CKD. ER is a cellular organelle devolved to protein biosynthesis and maturation, and cellular detoxification processes which are activated in response to an insult. This review aimed to dissect the cellular response to ER stress which manifests with activation of the unfolded protein response (UPR) with its major branches, namely PERK, IRE1α, ATF6 and the interplay between ER and mitochondria in the pathophysiology of kidney disease. Further, we will discuss the relationship between mediators of renal injury (with specific focus on vascular growth factors) and ER stress and UPR in the pathophysiology of both AKI and CKD with the aim to propose potential new targets for treatment for kidney disease.

Keywords: Endoplasmic reticulum stress; acute kidney injury; chronic kidney disease; unfolded protein response; vascular growth factors.