Characterization of Pancreatic Collagen-Expressing Fibroblasts in Mouse Acute Pancreatitis

Document Type

Journal Article

Publication Date

1-1-2025

Journal

Gastro hep advances

Volume

4

Issue

2

DOI

10.1016/j.gastha.2024.09.012

Keywords

Cell Depletion; Lineage Tracing; Mouse Model; Pancreatic Stellate Cells

Abstract

BACKGROUND AND AIMS: Pancreatic stellate cells (PSCs) are critical mediators in chronic pancreatitis with an undefined role in acute pancreatitis (AP). PSCs consist of a heterogenous group of cells and are considered interchangeable with pancreatic fibroblasts. This study explored the heterogeneous nature of PSCs by characterizing pancreatic collagen-expressing fibroblasts (PCFs) via lineage tracing in mouse normal and AP pancreas and determining the effect of PCF depletion in AP. METHODS: Tandem dimer Tomato (tdTom) PCFs in collagen type 1 (Col1)a2CreER mice receiving tamoxifen were characterized via fluorescence, Oil Red staining, and flow cytometry. AP was induced by cerulein, AP injury was assessed, and tdTom PCFs were monitored. The effect of PCF depletion on AP injury was evaluated in Col1a2CreER mice. RESULTS: Approximately 13% of pancreatic cells in Col1a2CreER mice were labeled by tdTom (tdTom PCFs), which surrounded acini, ducts, and blood vessels, and stained with Oil Red, collagen type I, vimentin, and desmin. tdTom PCFs increased 2-fold during AP, correlating with AP score, amylase, and alpha-smooth muscle actin and Ki67 staining. PCF depletion in Col1a2CreER mice receiving tamoxifen resulted in enhanced inflammation compared to control. CONCLUSION: PCFs may constitute a subset of PSCs and can be activated during AP. PCF depletion aggravates AP, suggesting a protective role for PCFs.

Department

Pathology

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