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TETRASPANIN18 REGULATES ANGIOGENESIS THROUGH
VEGFR2 AND NOTCH PATHWAYS
by
Xiuqing Li
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PATHOBIOLOGY)
August 2011
Copyright 2011 Xiuqing Li
Object Description
| Title | Tetraspanin18 regulates angiogenesis through VEGFR2 and notch pathways |
| Author | Li, Xiuqing |
| Author email | xiuqingl@usc.edu;espxli@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Pathobiology |
| School | Keck School of Medicine |
| Date defended/completed | 2011-06-14 |
| Date submitted | 2011-07-11 |
| Date approved | 2011-07-11 |
| Restricted until | 2012-07-11 |
| Date published | 2012-07-11 |
| Advisor (committee member) |
Gill, Parkash Hinton, David Maxson, Robert |
| Abstract | This work is to identify one of Tetraspanin family members, designated Tetraspanin18 (Tspan18), for expression in the developing blood vessels. Tspan18 knock down in zebrafish results in defective spouting, mis-patterning as well as regression of newly formed intersegmental vessels. Investigation of mechanism of action by global and targeted gene expression studies indicates that Tspan18 regulates VEGF/VEGFR2 and Notch/Dll4 pathways. Tspan18 knock down markedly reduced the expression of VEGF/VEGFR2 and downstream targets Notch, and EphrinB2 that are necessary for arterial phenotype and up-regulates EphB4 that defines venous phenotype. Conversely, Tspan18 knock down up-regulates Sema3ab/Nrp-plexinD1 which guide vessel positioning. Tspan18 deficient phenotype can be fully rescued by introduction of VEGFR2 or activated Notch while only partial rescue can be achieved with reduction of Semaphorin or PlexinD1. ❧ In vitro studies confirmed Tspan18 expressed in endothelial cells, and knock down resulted in loss of EC cell migration, invasion and tubular formation. Furthermore, Tspan18 knock down inhibits endothelial VEGFR2 and Notch expression and introduction of VEGFR2 or activated Notch corrected endothelial cell effects. Wound healing studies confirmed up-regulation of Tspan18 expression during remodeling and return to basal level within 7 days. Taken together, our findings reveal that Tspan18, a specific vessel marker, guide arterial development and modulate angiogenesis via VEGFR2 and Notch signaling pathways. |
| Keyword | Tetraspanin; VEGF; VEGF receptor; angiogenesis; Notch; Dll4 |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Li, Xiuqing |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume71/etd-LiXiuqing-71.pdf |
Description
| Title | Page 1 |
| Full text | TETRASPANIN18 REGULATES ANGIOGENESIS THROUGH VEGFR2 AND NOTCH PATHWAYS by Xiuqing Li A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PATHOBIOLOGY) August 2011 Copyright 2011 Xiuqing Li |
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