Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2015; 21(23): 7065-7073
Published online Jun 21, 2015. doi: 10.3748/wjg.v21.i23.7065
Neuropilins and liver
Gülsüm Özlem Elpek
Gülsüm Özlem Elpek, Department of Pathology, Medical School, Akdeniz University, Antalya 07070, Turkey
Author contributions: Elpek GÖ solely analyzed the data and wrote the paper.
Conflict-of-interest: The author declares that there are no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Gülsüm Özlem Elpek, MD, Professor, Department of Pathology, Medical School, Akdeniz University, Dumlupınar Bulvarı, Antalya 07070, Turkey. elpek@akdeniz.edu.tr
Telephone: +90-242-2496389 Fax: +90-242-2275540
Received: January 28, 2015
Peer-review started: January 28, 2015
First decision: March 10, 2015
Revised: March 23, 2015
Accepted: April 28, 2015
Article in press: April 28, 2015
Published online: June 21, 2015
Abstract

Neuropilins (NRPs) are highly conserved transmembrane glycoproteins that possess pleiotropic functions. Neuropilin-1 (NRP1) and its homologue neuropilin-2 interact as coreceptors with both class 3 semaphorins and vascular endothelial growth factor and are involved in neuronal guidance and angiogenesis, respectively. The contribution of NRPs to tumor angiogenesis has been highlighted in previous studies, leading to the development of NRP antagonists as novel anti-angiogenesis therapies. However, more recent studies have demonstrated that NRPs have a much broader spectrum of activity in the integration of different pathways in physiological and pathological conditions. A few studies investigated the role of NRPs in both malignant and non-neoplastic liver diseases. In normal liver, NRP1 is expressed in hepatic stellate cells and liver sinusoidal endothelial cells. NRP1 expression in hepatocytes has been associated with malignant transformation and may play an important role in tumor behavior. A contribution of NRPs in sinusoidal remodeling during liver regeneration has been also noted. Studies in chronic liver diseases have indicated that, besides its influence on angiogenesis, NRP1 might contribute to the progression of liver fibrosis owing to its effects on other growth factors, including transforming growth factor β1. As a result, NRP1 has been identified as a promising therapeutic target for future antifibrotic therapies based on the simultaneous blockade of multiple growth factor signaling pathways. In this review, the structure of NRPs and their interactions with various ligands and associated cell surface receptors are described briefly. The current understanding of the roles of the NRPs in liver diseases including tumors, regeneration and fibrogenesis, are also summarized.

Keywords: Neuropilins, Neuropilin-1, Neuropilin-2, Angiogenesis, Liver fibrosis, Vascular endothelial growth factor, Transforming growth factor β1

Core tip: The contribution of neuropilins (NRPs) to tumor angiogenesis has been identified in previous research, which has led to the development of NRP-targeted therapies. Although the number of relevant studies is too small to ascertain the precise role of NRPs in liver, the evidence implies an association with tumor behavior, liver regeneration and the progression of fibrosis. The interplay between NRPs and vascular endothelial growth factor, platelet-derived growth factor and transforming growth factor-β support NRPs as potential targets in the prevention of fibrogenesis in chronic liver diseases. However, further studies are needed to clarify whether NRPs may fill the large gaps in our understanding and ability to treat liver diseases.