Autophagy in HPCs modulates exosomal miRNAs to inhibit liver fibrosis

Frontiers JournalsSep 2 2024

The study investigates the role of autophagy in hepatic progenitor cells (HPCs) and its potential to modulate exosomal microRNAs (miRNAs) to inhibit liver fibrosis in the context of schistosomiasis, a disease caused by parasitic flatworms that can lead to severe organ damage, particularly to the liver.

Schistosomiasis-induced liver fibrosis is a significant health concern, with the disease affecting millions of people worldwide. The fibrotic process involves the excessive accumulation of extracellular matrix components, leading to the stiffening and dysfunction of the liver. The research explores the therapeutic potential of targeting autophagy, a cellular process involved in the degradation and recycling of cellular components, to mitigate this fibrotic response.

Autophagy has been implicated in various physiological and pathological conditions, including the regulation of immune responses and the clearance of damaged organelles. In the context of liver fibrosis, the study reveals that autophagy in HPCs can influence the secretion of exosomes containing specific miRNAs that target and reduce the fibrogenic activity of hepatic stellate cells (HSCs), another cell type involved in the fibrotic process.

The research employs both in vitro and in vivo models to examine the effects of autophagy modulation in HPCs. It demonstrates that the activation of autophagy in these cells leads to changes in the exosomal miRNA profile, with certain miRNAs being enriched in the exosomes released by HPCs. These exosomal miRNAs are then taken up by HSCs, where they exert anti-fibrotic effects by inhibiting the expression of key pro-fibrotic genes.

One of the key findings of the study is the identification of specific miRNAs that are associated with the anti-fibrotic effects of autophagy in HPCs. These miRNAs are shown to target genes involved in the transformation of HSCs from a quiescent state to an activated, fibrogenic state. By modulating the expression of these genes, the exosomal miRNAs from autophagy-activated HPCs can suppress the progression of liver fibrosis.

The study also investigates the molecular mechanisms underlying the regulation of autophagy in HPCs. It identifies several signaling pathways and transcription factors that are involved in the induction of autophagy and the subsequent changes in exosomal miRNAs. These findings provide insights into the complex regulatory networks that govern the crosstalk between HPCs and HSCs in the context of liver fibrosis.

The research highlights the potential therapeutic applications of modulating autophagy in HPCs for the treatment of liver fibrosis in schistosomiasis. By targeting specific miRNAs or the pathways that regulate autophagy, it may be possible to develop new strategies to prevent or reverse the fibrotic changes in the liver.

In conclusion, the study presents significant evidence for the role of autophagy in HPCs in modulating exosomal miRNAs to inhibit liver fibrosis in schistosomiasis. The findings contribute to the understanding of the cellular and molecular mechanisms underlying the pathogenesis of liver fibrosis and offer potential avenues for therapeutic intervention. Further research is needed to translate these findings into clinical applications and to explore the broader implications of targeting autophagy and exosomal miRNAs in other fibrotic diseases.