Abstract | OBJECTIVE: METHODS: PSCs were isolated from human pancreas tissues of patients undergoing operations for pancreatic cancer, and from rat pancreatic tissues. The effects of fibrinogen on key cell functions and activation of signalling pathways in PSCs were examined. RESULTS:
Fibrinogen induced the production of interleukin 6 ( IL6), interleukin 8 ( IL8), monocyte chemoattractant protein-1, vascular endothelial growth factor, angiopoietin-1 and type I collagen, but not proliferation or intercellular adhesion molecule-1 expression. Fibrinogen increased alpha-smooth muscle actin expression and induced the activation of nuclear factor-kappaB ( NF-kappaB), Akt and three classes of mitogen-activated protein kinases ( extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase and p38 mitogen-activated protein kinase (MAPK)). Fibrinogen-induced IL6 and IL8 production was inhibited by antibodies against alpha(v)beta(3) and alpha(5)beta(1) integrins, suggesting that these integrins worked as counter receptors for fibrinogen in PSCs. In addition, fibrinogen-induced production of these cytokines was abolished by an inhibitor of NF-kappaB, and partially inhibited by inhibitors of ERK and p38 MAPK. CONCLUSION:
Fibrinogen directly stimulated profibrogenic and proinflammatory functions in PSCs.
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Authors | A Masamune, K Kikuta, T Watanabe, K Satoh, M Hirota, S Hamada, T Shimosegawa |
Journal | Gut
(Gut)
Vol. 58
Issue 4
Pg. 550-9
(Apr 2009)
ISSN: 1468-3288 [Electronic] England |
PMID | 19052021
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Collagen Type I
- Cytokines
- Integrin alpha5beta1
- Integrin alphaVbeta3
- Interleukin-6
- Interleukin-8
- Peptide Fragments
- Procollagen
- procollagen type I carboxy terminal peptide
- Fibrinogen
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Topics |
- Animals
- Cell Movement
(physiology)
- Cells, Cultured
- Collagen Type I
(biosynthesis)
- Cytokines
(biosynthesis)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Fibrinogen
(metabolism, pharmacology)
- Humans
- Integrin alpha5beta1
(physiology)
- Integrin alphaVbeta3
(physiology)
- Interleukin-6
(biosynthesis)
- Interleukin-8
(biosynthesis)
- Male
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Pancreas
(cytology, drug effects, metabolism, pathology)
- Pancreatic Neoplasms
(metabolism, pathology)
- Pancreatitis, Chronic
(metabolism, pathology)
- Peptide Fragments
(biosynthesis)
- Procollagen
(biosynthesis)
- Rats
- Rats, Wistar
- Signal Transduction
(drug effects, physiology)
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