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Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1.
- Source :
-
The American journal of pathology [Am J Pathol] 2011 Dec; Vol. 179 (6), pp. 2990-9. Date of Electronic Publication: 2011 Sep 28. - Publication Year :
- 2011
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Abstract
- Pigment epithelium-derived factor (PEDF) is important for maintaining the normal extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild-type mice fed either a control or ethanol diet using an intragastric feeding model. Pancreatitis responses were elicited with either a single episode or a repetitive cerulein-induced (50 μg/kg, 6 hourly i.p. injections) protocol in wild-type and PEDF-null mice. Quantitative real-time PCR and immunoblotting were performed to assess fibrogenic responses. In wild-type animals, PEDF expression increased with pancreatitis and was more pronounced in mice fed ethanol. Compared with wild-type mice, α-smooth muscle actin staining and expression levels of fibrogenic markers (eg, transforming growth factor-β1, platelet-derived growth factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wild-type pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved with longer recovery periods. PEDF overexpression suppressed thrombospondin-1 levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF expression in wild-type mice. PEDF-null mice, however, demonstrated enhanced early fibrotic responses compared with wild-type mice with pancreatitis. These findings indicate that PEDF acts as a compensatory antifibrotic cytokine in pancreatitis.<br /> (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Ceruletide toxicity
Collagen Type I metabolism
Extracellular Matrix metabolism
Fibrosis
Mice
Mice, Inbred C57BL
Nerve Growth Factors deficiency
Pancreatitis chemically induced
Pancreatitis pathology
Platelet-Derived Growth Factor metabolism
RNA, Messenger metabolism
Serpins deficiency
Thrombospondin 1 metabolism
Transforming Growth Factor beta1 metabolism
Eye Proteins physiology
Nerve Growth Factors physiology
Pancreas pathology
Serpins physiology
Thrombospondin 1 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 179
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 21964188
- Full Text :
- https://doi.org/10.1016/j.ajpath.2011.08.009