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http://hdl.handle.net/11375/11361
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DC Field | Value | Language |
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dc.contributor.advisor | Krepinsky, Joan | en_US |
dc.contributor.author | Sukumar, Aravin | en_US |
dc.date.accessioned | 2014-06-18T16:54:25Z | - |
dc.date.available | 2014-06-18T16:54:25Z | - |
dc.date.created | 2011-09-28 | en_US |
dc.date.issued | 2011-10 | en_US |
dc.identifier.other | opendissertations/6333 | en_US |
dc.identifier.other | 7391 | en_US |
dc.identifier.other | 2263918 | en_US |
dc.identifier.uri | http://hdl.handle.net/11375/11361 | - |
dc.description.abstract | <p>Glomerulosclerosis (GS) is the irreversible scarring of glomerular tissue which underlies the development of chronic kidney disease (CKD). Increased intraglomerular capillary pressure (P<sub>gc</sub>) is a major contributor to the development of GS and can occur in both hypertensive and diabetic patients. With elevated P<sub>gc</sub>, <em>in vitro</em> and <em>in vivo</em> evidence suggest that mesangial cells (MC) experience cyclic stretch and secrete pro-fibrotic factors such as connective tissue growth factor (CTGF) which contributes to GS. The signaling pathways that are activated in response to elevated P<sub>gc</sub> and lead to extracellular matrix (ECM) production in MCs are the main focus of this thesis.</p> <p>Previous data demonstrated activation of the Rho GTPase, Rac1, with cyclic stretch in MCs. Furthermore, the most characterized effector of Rac1, p21-activated kinase (PAK), has been observed to have a role in endothelial cells (ECs) exposed to mechanical stress. We thus proposed that the Rac1-PAK signaling pathway is involved in mechanical stress signaling in MCs.</p> <p>Our data demonstrate that Rac1-PAK signaling was activated in response to cyclic stretch and required for stretch-induced CTGF production in MCs. RhoA activation was also regulated by Rac1-PAK signaling, and RhoA/ROCK were observed to mediate CTGF upregulation with stretch. Further investigation on the role of Rac1-PAK signaling and how it regulates CTGF in MCs exposed to stretch, will provide insight into potential therapeutic targets to delay the progression of hypertension-mediated CKD.</p> | en_US |
dc.subject | mesangial cells | en_US |
dc.subject | mechanical stress | en_US |
dc.subject | p21-activated kinase | en_US |
dc.subject | fibrosis | en_US |
dc.subject | renal disease | en_US |
dc.subject | connective tissue growth factor | en_US |
dc.subject | Medical Cell Biology | en_US |
dc.subject | Medical Cell Biology | en_US |
dc.title | The Role of p21-Activated Kinase in Mechanical Stress-Induced Connective Tissue Growth Factor Upregulation in Mesangial Cells | en_US |
dc.type | thesis | en_US |
dc.contributor.department | Health Sciences | en_US |
dc.description.degree | Master of Science in Medical Sciences (MSMS) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Size | Format | |
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fulltext.pdf | 1.77 MB | Adobe PDF | View/Open |
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