Pathogenesis of Renal Fibrosis: a Role for Proteinase-activated Receptor-2
| atmire.migration.oldid | 707 | |
| dc.contributor.advisor | Hollenberg, Morley | |
| dc.contributor.advisor | Muruve, Daniel | |
| dc.contributor.author | Chung, Hyun Jae | |
| dc.date.accessioned | 2013-01-28T15:49:49Z | |
| dc.date.available | 2013-06-15T07:01:34Z | |
| dc.date.issued | 2013-01-28 | |
| dc.date.submitted | 2013 | en |
| dc.description.abstract | Renal fibrosis is the final manifestation of all progressive chronic kidney disease with a significant morbidity and mortality. However, the underlying mechanisms remain largely unknown. Proteinase-activated Receptor-2 (PAR2) is a G-protein-coupled receptor that is proteolytically activated by serine proteinases such as trypsin. In our in vitro studies, we found that stimulation of PAR2 in human proximal tubular cells with PAR2-activating peptide alone significantly upregulated expression of CCN2 and did so synergistically to augment Transforming growth factor-β (TGF-β)-induced CCN2 production. This synergy was reduced by MAPKinase inhibition. We also found that PAR2 deficiency in mice with unilateral ureteral obstruction (UUO) significantly reduced tubular injuries and fibrosis, and synthesis of renal collagen and α-smooth muscle actin at 7 days post UUO. Our findings demonstrate the potential contribution of PAR2 to renal injury and fibrosis at an early time point due to the ability of PAR2 to augment the production of a profibrotic cytokine. | en_US |
| dc.identifier.citation | Chung, H. J. (2013). Pathogenesis of Renal Fibrosis: a Role for Proteinase-activated Receptor-2 (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27270 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/27270 | |
| dc.identifier.uri | http://hdl.handle.net/11023/515 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Pathology | |
| dc.subject.classification | Fibrosis | en_US |
| dc.subject.classification | PAR2 | en_US |
| dc.subject.classification | kidney | en_US |
| dc.subject.classification | TGF-beta | en_US |
| dc.subject.classification | CTGF | en_US |
| dc.title | Pathogenesis of Renal Fibrosis: a Role for Proteinase-activated Receptor-2 | |
| dc.type | master thesis | |
| thesis.degree.discipline | Medical Science | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Master of Science (MSc) | |
| ucalgary.item.requestcopy | true |