Characterization of Pancreatic Collagen-Expressing Fibroblasts in Mouse Acute Pancreatitis

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.