Exosomal miR‐103‐3p from LPS‐activated THP‐1 macrophage contributes to the activation of hepatic stellate cells

Abstract

Hepatic fibrosis occurs during chronic hepatic injury and is involved in hepatic stellate cells (HSCs) activated by several types of immune cells. Among the immune cells, hepatic macrophages and their crosstalk with HSCs play a vital role in all stages of hepatic fibrosis. Exosomes, which are 30‐150 nm lipid bilayer vehicles, can transfer specific lipid, nucleic acids, proteins, and other bioactive molecules. Exosomes can act as good communication between macrophages and HSCs. Herein, we investigated the role of exosomes between THP‐1 macrophage and HSCs in the progression of liver fibrosis. Exosomes originating from lipopolysaccharide (LPS)‐treated THP‐1 macrophages promoted HSCs proliferation and induced the increased expression of fibrotic genes. LPS could alter the miRNA profile in exosomes secreted from THP‐1 macrophages. The changed miR‐103‐3p in exosomes could promote HSCs proliferation and activation by targeting Krüppel‐like factor 4 (KLF4) and it plays important roles in the crosstalk between THP‐1 macrophages and HSCs during the progression of liver fibrosis. Moreover, miR‐103‐3p in serum exosomes from liver fibrosis patients could be a biomarker for liver fibrosis. Therefore, exosomes may have important roles in the crosstalk between macrophage and HSCs in the progression of chronic liver diseases.

MiR-27a-3p suppresses cerebral ischemia-reperfusion injury by targeting FOXO1

“…MiRNAs exert their effects by suppressing expression of their target genes [ 19 , 20 ]. In the present study, luciferase reporter assays revealed FOXO1 to be a direct target gene of miR-27a-3p in CI/R.…”

Autophagy Regulates the Effects of Adipose-derived Stem Cells Exosomes on Lipopolysaccharide-induced Pulmonary Microvascular Barrier Damage

“…Ischemic preconditioning can potentiate the protective effect of marrow stromal cells-derived exosomes on endotoxin-induced acute lung injury [28]. In addition, LPS pretreatment not only induced exosome secretion by macrophages but also enhanced the effects of macrophage-derived exosomes on the proliferation and activation of hepatic stellate cells [29]. Similarly, in the present study, we showed that preconditioning with IL-1β, one of the key proin ammatory factors induced by LPS, promoted the production of ADSC-Exos and affected the expression of miRNAs in exosomes.…”

Exosomes in Sepsis

“…Exosomal miR-155, a micro-RNA with pro-inflammatory activity, was elevated in the liver of mice subjected to LPS and/or the TLR9 ligand cytidine-phosphate-guanosine (CpG), suggesting its contribution to liver dysfunction ( 71 ). Exosomes might also contribute to chronic liver dysfunction after sepsis, as exosomal miR-103-3p from LPS-activated macrophages targeted Krüppel-like factor 4 (KLF4) to increase α-SMA, TGF-β, and Col1a1 of hepatic stellate cells, which can contribute to liver fibrosis ( 72 ). As a whole, exosomes induce acute and chronic liver dysfunction in sepsis by inducing local inflammation and remodeling, respectively.…”