Renalase: A multifunctional protein

Renalase is a protein mainly found in the kidneys. It is also found in the myocardium, adipose tissue, liver, peripheral and central nervous systems, small intestine, and skeletal muscles.

This protein has been discovered recently. Not much is known, but it is considered a multifunctional protein because of its involvement in several mechanisms of the body, including hypertension, cardiac function, kidney diseases, diabetes, and in cancer.

Dr. Anupama Vijayakumar
Prof. Nitish R. Mahapatra

In this review article, written by Dr. Anupama Vijayakumar and Prof. Nitish R. Mahapatra, from the Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology (IIT) Madras, Chennai, India, the role and function of renalase, especially with regard to hypertension and renal activity were discussed in detail.

In the case of hypertension, it is thought that catecholamines (a class of neurotransmitters) are catalytically degraded by renalase thus resulting in lowered blood pressure and heart rate. Thus renalase supplementation is regarded as an attractive candidate to treat hypertension although further studies are required.

Studies on renalase also reveal that it could act as a signalling molecule, or a cytokine, and as an anomerase (an enzyme that catalyses the formation of certain sugar molecules). It is also considered to be a factor in diabetes, lipid metabolism, and cancer. In these cases, it is thought that the modulation of renalase would be better to cure these diseases.

Even so, the debate still continues as to whether renalase is a “causative factor or just an innocent bystander”.  

Three transcription (transcription is the process by which DNA is converted to RNA) factors namely, Sp1, STAT3, and ZBP89 were reported previously by Prof Mahapatra’s lab as the key molecular factors in the regulation of human renalase gene expression.

It was also found that renalase is under the post-transcriptional regulation of two microRNAs, namely, miR-29b and miR-146a. Further, it is regarded as having a function in COVID-19. Renalase was found to be diminished in patients infected with this virus.

Further research is required to understand the role and function of renalase. A major impediment to the proper understanding of renalase is the clear divergence in the literature regarding the basic biochemical functions of renalase, in both its catecholamine-metabolizing activity and its function as an enzyme or a cytokine. Further studies in large populations with different ethnicities are required to confirm the associations between renalase genetic variants and cardiometabolic/renal disease states.

The authors of this paper feel renalase should be given importance and studied in detail. The physiological and biochemical properties of renalase should be studied so that its various therapeutic potentials can be harnessed.

Dr. K. Shivakumar, ICMR Emeritus Scientist, from the Department of Biotechnology, University of Kerala, Trivandrum, India, gave his analysis on this review, and stressed its importance with the following comments: “This review by Anupama Vijayakumar and Nitish R Mahapatra attempts to comprehend the role of renalase in cardiometabolic disorders. Discovered less than two decades ago, renalase is an enzyme or hormone that can act as a cytokine, an anomerase or oxidase. Expressed mainly in the kidneys, renalase is reported to have a hypotensive effect through regulation of sympathetic tone, and in addition, has been implicated in multiple aspects of myocardial pathophysiology. The article discusses renalase-mediated mechanisms of blood pressure regulation and the manifold roles of renalase in cardiac hypertrophy, ventricular remodelling and atherosclerosis. Further, the role of renalase in combating renal injury has been elucidated, highlighting the underlying mechanisms. Refreshingly, without limiting the review to cardiovascular and renal pathophysiology, the authors do well to dwell upon its potential role in cancer, consistent with the current view that cancer is a metabolic disorder. Aptly terming renalase “a new kid on the block”, the authors submit that proof-of-concept studies should be undertaken to uncover the physiological and biochemical properties of renalase, which may pave the way to novel therapies that target renalase to manage cardiometabolic disorders. Overall, this review is a repository of useful information for investigators across a spectrum of disciplines.”

Article by Akshay Anantharaman
Here is the original link to the paper:



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