Work

Characterization of Pancreatic Collagen-Expressing Fibroblasts in Mouse Acute Pancreatitis

Year: 2024

Type: article

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 tdTomato (Tom) 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 diphtheria toxin A mice. Results Approximately 13% of pancreatic cells in Col1a2CreER Tom 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 diphtheria toxin A 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.

Source: Gastro Hep Advances

DOI: 10.1016/j.gastha.2024.09.012