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MECHANOTRANSDUCTION AND EPIDERMAL GROWTH FACTOR RECEPTOR SIGNALING IN BLADDER EPITHELIUM

Balestreire, Elena Marie (2007) MECHANOTRANSDUCTION AND EPIDERMAL GROWTH FACTOR RECEPTOR SIGNALING IN BLADDER EPITHELIUM. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

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.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Balestreire, Elena Marieemb57@pitt.eduEMB57
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKleyman, ThomasKleyman@dom.pitt.eduKLEYMAN
Committee MemberApodaca, Gerardgla6@pitt.eduGLA6
Committee MemberBrodsky, Jeffreyjbrodsky@pitt.eduJBRODSKY
Committee MemberTraub, Lintontraub@pitt.eduTRAUB
Committee MemberBirder, Lorilbirder@pitt.eduLBIRDER
Committee MemberHughey, RebeccaHughey@dom.pitt.eduHUGHEYR
Date: 27 June 2007
Date Type: Completion
Defense Date: 4 June 2007
Approval Date: 27 June 2007
Submission Date: 21 June 2007
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: bladder; capacitance; EGF; EGFR; epidermal growth factor; epidermal growth factor receptor; epithelium; exocytosis; exocytosis; HB-EGF; MAP kinase; mechanical; mechanotransduction; membrane traffic; membrane trafficking; pressure; stretch; surface area; uroepithelium; urothelium; Ussing chamber
Other ID: http://etd.library.pitt.edu/ETD/available/etd-06212007-094510/, etd-06212007-094510
Date Deposited: 10 Nov 2011 19:48
Last Modified: 15 Nov 2016 13:44
URI: http://d-scholarship.pitt.edu/id/eprint/8157

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