In response to changes in intralumenal pressure, the urinary bladder modulates its mucosal surface to accommodate a wide range of urine volumes upon filling and voiding. During bladder stretch, umbrella cells that line the mucosal surface of the bladder undergo changes in surface area mediated by the exocytosis and endocytosis of subapical discoidal vesicles. While a number of signaling factors are required for this process, how these signals interact with each other and whether they are integrated in any manner is not known. The identification of the epidermal growth factor receptor (EGFR) as an apical receptor for stretch-induced HB-EGF signaling provides a previously unrecognized function for this versatile receptor in bladder physiology. It appears that the EGFR signaling is able to regulate protein synthesis via a MAPK signaling pathway, which is required for the late response of the tissue to prolonged stretch. The transactivation of EGFR via a metalloproteinase-dependent pathway opens the possibility that several previously recognized stretch-induced signals function upstream to stimulate EGFR activity in an integrated signaling pathway. The importance of tight regulation of EGFR activity in the bladder is highlighted by its role in bladder carcinoma pathophysiology, and future studies of this pathway may provide insights that lead to diagnostic and therapeutic advances.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06212007-094510 |
| Date | 27 June 2007 |
| Creators | Balestreire, Elena Marie |
| Contributors | Gerard Apodaca, Ph.D., Linton Traub, Ph.D., Thomas Kleyman, M.D., Lori Birder, Ph.D., Rebecca Hughey, Ph.D., Jeffrey Brodsky, Ph.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-06212007-094510/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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