Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis

Haber, P. S., Keogh, G. W., Apte, M. V., Moran, C. S., Stewart, N. L., Crawford, D. H. G., Pirola, R. C., McCaughan, G. W., Ramm, G. A. and Wilson, J. S. (1999) Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis. American Journal of Pathology, 155 4: 1087-1095.


Author Haber, P. S.
Keogh, G. W.
Apte, M. V.
Moran, C. S.
Stewart, N. L.
Crawford, D. H. G.
Pirola, R. C.
McCaughan, G. W.
Ramm, G. A.
Wilson, J. S.
Title Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis
Journal name American Journal of Pathology   Check publisher's open access policy
Publication date 1999-10
Sub-type Article
DOI 10.1016/S0002-9440(10)65211-X
Volume number 155
Issue number 4
ISSN 0002-9440
Start page 1087
End page 1095
Total pages 9
Place of publication Baltimore, MD, USA
Publisher American Society of Investigative Pathology
Collection year 1999
Language eng
Subject C1
321006 Gastroenterology and Hepatology
730113 Digestive system and disorders
Abstract 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 pan creatic 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 alpha-smooth muscle actin (alpha SMA), desmin, and platelet-derived growth factor receptor type beta (PDGFR beta). The relationship of fibrosis to stellate cell activation was studied by staining of serial sections for alpha SMA, desmin, PDGFR beta, and collagen, and by dual-staining for alpha SMA plus either Sirius Red or in situ hybridization for procollagen alpha(1) (I) mRNA. The cellular source of TGF beta 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 alpha SMA-positive cells. alpha SMA staining colocallzed with procollagen alpha(1) (I) mRNA expression. In the rat model, desmin staining was associated with PDGFR beta in areas of fibrosis. TGF beta 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.
Keyword Pathology
Fat-storing Cells
Transforming Growth Factor-beta(1)
Hepatic-fibrosis
Expression
Rat
Fibrogenesis
Liver
Growth-factor-beta-1
Mechanisms
Collagen
Q-Index Code C1

Document type: Journal Article
Sub-type: Article
Collection: School of Medicine Publications
 
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