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Activation of Pancreatic Stellate Cells in Human and Experimental Pancreatic Fibrosis

https://doi.org/10.1016/S0002-9440(10)65211-XGet rights and content

The mechanisms of pancreatic fibrosis are poorly understood. In the liver, stellate cells play an important role in fibrogenesis. Similar cells have recently been isolated from the pancreas and are termed pancreatic stellate cells. The aim of this study was to determine whether pancreatic stellate cell activation occurs during experimental and human pancreatic fibrosis. Pancreatic fibrosis was induced in rats (n = 24) by infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct. Surgical specimens were obtained from patients with chronic pancreatitis (n = 6). Pancreatic fibrosis was assessed using the Sirius Red stain and immunohistochemistry for collagen type I. Pancreatic stellate cell activation was assessed by staining for α-smooth muscle actin (αSMA), desmin, and platelet-derived growth factor receptor type β (PDGFRβ). The relationship of fibrosis to stellate cell activation was studied by staining of serial sections for αSMA, desmin, PDGFRβ, and collagen, and by dual-staining for αSMA plus either Sirius Red or in situ hybridization for procollagen α1 (I) mRNA. The cellular source of TGFβ was examined by immunohistochemistry. The histological appearances in the TNBS model resembled those found in human chronic pancreatitis. Areas of pancreatic fibrosis stained positively for Sirius Red and collagen type I. Sirius Red staining was associated with αSMA-positive cells. αSMA staining colocalized with procollagen α1 (I) mRNA expression. In the rat model, desmin staining was associated with PDGFRβ in areas of fibrosis. TGFβ was maximal in acinar cells adjacent to areas of fibrosis and spindle cells within fibrotic bands. Pancreatic stellate cell activation is associated with fibrosis in both human pancreas and in an animal model. These cells appear to play an important role in pancreatic fibrogenesis.

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Supported by research grants from the Gastroenterological Society of Australia, the National Health and Medical Research Council of Australia, the Department of Veterans’ Affairs, and the Clive and Vera Ramaciotti Foundation.

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