The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis

Abstract

Background: Hepatic stellate cells (HSCs) are the central players interacting with multiple cell types in liver fibrosis. The crosstalk between HSCs and macrophages has recently become clearer. Irisin, an exercise-responsive myokine, was known to have a potentially protective role in liver and renal fibrosis, especially in connection with stellate cells. This study investigated the effects of irisin on the interaction between HSCs and macrophages. Methods: Tamm-Horsfall protein-1 (THP-1) human monocytes were differentiated into macrophages, polarized into the inflammatory M1 phenotype with lipopolysaccharide. Lieming Xu-2 (LX-2) cells, human HSCs, were treated with conditioned media (CM) from M1 macrophages, with or without recombinant irisin. HSCs responses to CM from M1 macrophages were evaluated regarding activation, proliferation, wound healing, trans-well migration, contractility, and related signaling pathway. Results: CM from M1 macrophages significantly promoted HSC proliferation, wound healing, transwell migration, and contractility, but not activation of HSCs. Irisin co-treatment attenuated these responses of HSCs to CM. However, CM and irisin treatment did not induce any changes in HSC activation. Further, irisin co-treatment alleviated CM-induced increase of phopho-protein kinase B (pAKT), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1). Conclusion: These findings suggested that irisin may play a protective role in the pathogenesis of liver fibrosis, especially when working in the crosstalk between HSCs and macrophages.

SKIL/SnoN attenuates TGF-β1/SMAD signaling-dependent collagen synthesis in hepatic fibrosis

“…As a member of the TIMP family, TIMP-1 is a natural inhibitor of matrix metalloproteinases [ 29 ]. In addition to its inhibitory role against MMPs, the encoded protein is able to promote cell proliferation in hepatic cells, participate in the migration of HSCs, and have an anti-apoptotic function [ 31 , 32 ]. As a member of the MMP family, MMP-13 is involved in the breakdown of ECM in the process of HF [ 33 , 34 ].…”

The effect of sarcopenia and serum myokines on prognosis and survival in cirrhotic patients: a multicenter cross-sectional study

“…We think that the substantial difference between clinical and pathological scoring systems may be responsible for this result. As an exercise-responsive myokine, irisin is known to have a potentially protective role in liver fibrosis [43]. On the contrary, serum myostatin levels were reported to be increased with the progression of liver fibrosis and liver fibroblasts were shown to be activated and produced collagen following stimulation with myostatin [44].…”