Nature Nanotechnology: Relaxin relieves liver fibrosis through liver macrophage exosomes

Exosomes are small vesicles with a diameter of about 30-150 nm secreted by living cells.

Activated hepatic stellate cells (aHSCs) are the main effector cells of liver fibrosis, which respond to chronic liver injury by producing excessive extracellular matrix (ECM).

Using nanoparticle-mediated delivery, Professor Huang Lifu’s team found that although enhancing the expression of relaxin in fibrotic liver in vivo has a strong anti-fibrotic effect, in vitro treatment cannot reverse the static phenotype of activated hepatic stellate cells , Indicating that the microenvironment surrounding aHSCs promotes relaxin-mediated anti-fibrosis.

Specifically, the expression of miR-30a-5p in exosomes secreted by relaxin-treated macrophages is up-regulated, and after being absorbed by aHSCs, it targets apoptotic signal-regulated kinase 1 (ASK1), and it can also fight against aHSCs to promote fibrosis Insufficient expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) caused by activation.

Relaxin-induced macrophage exosomes miR-30a-5p inactivate aHSCs by targeting ASK1

In conclusion, this study describes the sequential steps of relaxin-induced phenotypic switching of macrophages, highlights the key role of macrophages in relaxin-induced remission of liver fibrosis, and reveals anti-fibrotic macrophages and aHSCs The crosstalk relationship between the two provides a combination gene therapy (pRLN+miR-30a-5p) that can safely and effectively improve liver fibrosis.

Step model of relaxin gene therapy in liver anti-fibrosis

Original source:

HuM, et al.