| dc.contributor.author | Isbrucker, Richard Allan. | en_US |
| dc.date.accessioned | 2014-10-21T12:36:36Z | |
| dc.date.available | 1997 | |
| dc.date.issued | 1997 | en_US |
| dc.identifier.other | AAINQ24774 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55515 | |
| dc.description | Proliferation of fibroblasts and accumulation of extracellular matrix are two hallmarks of fibrotic liver disease. Hepatic stellate cells are the major collagen producing cells of the liver and are transformed into proliferative myofibroblasts following activation by cytokines. Whether myofibroblast proliferation and extracellular matrix production are regulated by the same cytokines is not known. An increase in total collagenous protein within the liver has been reported in several animal models of fibrosis including the yellow phosphorus induced swine model of hepatic fibrosis used in this thesis. Northern blot analysis of total RNA isolated from yellow phosphorus induced fibrotic pig liver show increased mRNA levels for collagens $\alpha$1(I) and $\alpha$1(III) at 8 and 12 weeks following the commencement of yellow phosphorus administration when compared to control pigs. Monocyte-conditioned medium from these fibrotic pigs induced collagen production by cultured porcine myofibroblasts which was reduced by pre-incubation with PDGF B/B antibody. Administration of pentoxifylline, concurrently with yellow phosphorus, to fibrotic pigs during the 8 to 12 week period decreased the mRNA levels for collagens $\alpha$1(I) and $\alpha$1(III). PDGF, which was previously shown to stimulate proliferation of non-confluent fibroblasts, is shown to induce both proliferation and collagen production in porcine myofibroblasts but that these two events are independent and can occur without the presence of the other. Pentoxifylline and its metabolite, M-1, inhibit PDGF-stimulated collagen production in cultured porcine myofibroblasts, but that these effects are not mimicked by elevations in intracellular cAMP. These results demonstrate the importance of PDGF in the development of liver fibrosis and provides evidence for the mechanism of pentoxifylline in reducing liver fibrosis. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1997. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Pharmacology. | en_US |
| dc.subject | Biology, Animal Physiology. | en_US |
| dc.subject | Health Sciences, Pathology. | en_US |
| dc.title | Platelet-derived growth factor and pentoxifylline modulation of collagen synthesis in vivo and in vitro. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
