Origin of myofibroblasts in the fibrotic liver in mice

TLDR

Activated hepatic stellate cells and portal fibroblasts are the main sources of liver scar tissue, yet the role of portal fibroblasts in cholestatic fibrosis remains poorly defined because of purification challenges and missing specific markers. The study aims to determine whether portal fibroblasts contribute to cholestatic liver fibrosis and to identify the mechanisms of their activation. A flow‑cytometry purification protocol was established using collagen‑α1(I)-GFP mice, enabling isolation of portal fibroblasts and identification of candidate specific markers. The method yielded purified portal fibroblasts and revealed several candidate aPF‑specific markers.

Abstract

Significance Liver resident activated hepatic stellate cells (aHSCs), and activated portal fibroblasts (aPFs) are the major source of the fibrous scar in the liver. aPFs have been implicated in liver fibrosis caused by cholestatic liver injury, whereas fibrosis in hepatotoxic liver injury is attributed to aHSCs. However, the contribution of aPFs to cholestatic fibrosis is not well characterized because of difficulties in cell purification and the lack of identified aPF-specific markers. We have developed a novel flow cytometry-based method of aPFs purification from the nonparenchymal cell fraction of collagen-α1(I)-GFP mice and have identified potential aPF-specific markers. The goal of this study is to determine whether aPFs contribute to cholestatic liver fibrosis and identify the mechanism(s) of their activation.