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http://hdl.handle.net/11375/11361
Title: | The Role of p21-Activated Kinase in Mechanical Stress-Induced Connective Tissue Growth Factor Upregulation in Mesangial Cells |
Authors: | Sukumar, Aravin |
Advisor: | Krepinsky, Joan |
Department: | Health Sciences |
Keywords: | mesangial cells;mechanical stress;p21-activated kinase;fibrosis;renal disease;connective tissue growth factor;Medical Cell Biology;Medical Cell Biology |
Publication Date: | Oct-2011 |
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> |
URI: | http://hdl.handle.net/11375/11361 |
Identifier: | opendissertations/6333 7391 2263918 |
Appears in Collections: | Open Access Dissertations and Theses |
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fulltext.pdf | 1.77 MB | Adobe PDF | View/Open |
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