Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2020; 26(10): 1005-1019
Published online Mar 14, 2020. doi: 10.3748/wjg.v26.i10.1005
Role of spleen tyrosine kinase in liver diseases
Dhadhang Wahyu Kurniawan, Gert Storm, Jai Prakash, Ruchi Bansal
Dhadhang Wahyu Kurniawan, Gert Storm, Jai Prakash, Ruchi Bansal, Department of Biomaterials Science and Technology, Faculty of Science and Technology, Technical Medical Centre, University of Twente, Enschede 7500, the Netherlands
Dhadhang Wahyu Kurniawan, Department of Pharmacy, Universitas Jenderal Soedirman, Purwokerto 53132, Indonesia
Gert Storm, Department of Pharmaceutics, University of Utrecht, Utrecht 3454, the Netherlands
Ruchi Bansal, Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen, Enschede 7500, the Netherlands
Author contributions: Kurniawan DW drafted and wrote the review; Bansal R critically reviewed and revised the review; Storm G and Prakash J read the review and provided their feedback; All the authors have read the review, contributed in language editing, and approved the final version.
Supported by the Endowment Fund for the Education Republic of Indonesia (Lembaga Pengelola Dana Pendidikan/LPDP RI), No. 44/LPDP/2015.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
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:
Corresponding author: Ruchi Bansal, PhD, Assistant Professor, Department of Biomaterials Science and Technology, Technical Medical Centre, Faculty of Science and Technology, Zuidhorst 245, University of Twente, Enschede 7500, the Netherlands.
Received: November 29, 2019
Peer-review started: November 29, 2019
First decision: January 7, 2020
Revised: January 14, 2020
Accepted: February 28, 2020
Article in press: February 28, 2020
Published online: March 14, 2020

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase expressed in most hematopoietic cells and non-hematopoietic cells and play a crucial role in both immune and non-immune biological responses. SYK mediate diverse cellular responses via an immune-receptor tyrosine-based activation motifs (ITAMs)-dependent signalling pathways, ITAMs-independent and ITAMs-semi-dependent signalling pathways. In liver, SYK expression has been observed in parenchymal (hepatocytes) and non-parenchymal cells (hepatic stellate cells and Kupffer cells), and found to be positively correlated with the disease severity. The implication of SYK pathway has been reported in different liver diseases including liver fibrosis, viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis and hepatocellular carcinoma. Antagonism of SYK pathway using kinase inhibitors have shown to attenuate the progression of liver diseases thereby suggesting SYK as a highly promising therapeutic target. This review summarizes the current understanding of SYK and its therapeutic implication in liver diseases.

Keywords: Spleen tyrosine kinase, Liver diseases, Inflammation, Targeted therapeutics, Spleen tyrosine kinase inhibitors

Core tip: Spleen tyrosine kinase has reported to be positively correlated with disease severity and has shown to play a crucial role in the pathogenesis of liver diseases. Therefore, specific targeting of spleen tyrosine kinase pathway using kinase inhibitors is a highly promising therapeutic approach for the treatment of liver diseases.