Characterization of Pancreatic Collagen-Expressing Fibroblasts in Mouse Acute Pancreatitis

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.