Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2021; 27(24): 3516-3529
Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3516
Neuropilin-1: A feasible link between liver pathologies and COVID-19
Aitor Benedicto, Iñigo García-Kamiruaga, Beatriz Arteta
Aitor Benedicto, Beatriz Arteta, Department of Cellular Biology and Histology, School of Medicine and Nursing, University of the Basque Country, Leioa 48940, Bizkaia, Spain
Iñigo García-Kamiruaga, Department of Gastroenterology and Hepatology, San Eloy Hospital, Barakaldo 48902, Spain
Author contributions: Benedicto A and Arteta B designed the review concept; Benedicto A, García-Kamiruaga and Arteta B wrote the manuscript.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Aitor Benedicto, PhD, Assistant Lecturer, Doctor, Department of Cellular Biology and Histology, School of Medicine and Nursing, University of the Basque Country, Barrio Sarriena s/n, Leioa 48940, Bizkaia, Spain. aitor.benedicto@ehu.es
Received: February 28, 2021
Peer-review started: February 28, 2021
First decision: March 27, 2021
Revised: April 16, 2021
Accepted: May 25, 2021
Article in press: May 25, 2021
Published online: June 28, 2021
Processing time: 116 Days and 12.8 Hours
Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a tremendous impact on the health of millions of people worldwide. Unfortunately, those suffering from previous pathological conditions are more vulnerable and tend to develop more severe disease upon infection with the new SARS-CoV-2. This coronavirus interacts with the angiotensin-converting enzyme 2 receptor to invade the cells. Recently, another receptor, neuropilin-1 (NRP-1), has been reported to amplify the viral infection. Interestingly, NRP-1 is expressed in nonparenchymal liver cells and is related to and upregulated in a wide variety of liver-related pathologies. It has been observed that SARS-CoV-2 infection promotes liver injury through several pathways that may be influenced by the previous pathological status of the patient and liver expression of NRP-1. Moreover, coronavirus disease 2019 causes an inflammatory cascade called cytokine storm in patients with severe disease. This cytokine storm may influence liver sinusoidal-cell phenotype, facilitating viral invasion. In this review, the shreds of evidence linking NRP-1 with liver pathologies such as hepatocellular carcinoma, liver fibrosis, nonalcoholic fatty liver disease and inflammatory disorders are discussed in the context of SARS-CoV-2 infection. In addition, the involvement of the infection-related cytokine storm in NRP-1 overexpression and the subsequent increased risk of SARS-CoV-2 infection are also analyzed. This review aims to shed some light on the involvement of liver NRP-1 during SARS-CoV-2 infection and emphasizes the possible involvement this receptor with the observed liver damage.

Keywords: Liver; Liver sinusoidal endothelial cells; Hepatic stellate cells; SARS-CoV-2; COVID-19; Pathology

Core Tip: Severe acute respiratory syndrome coronavirus 2 uses angiotensin-converting enzyme 2 and neuropilin-1 (NRP-1) receptors to infect cells. NRP-1 expression is upregulated in several liver pathologies, which may facilitate viral infection. Moreover, the cytokine storm might increase liver permeability and NRP-1 expression, giving rise to an increased severity of infection and a worse prognosis.