Localized HB-EGF signaling and Connexin43 decrease in the myocardium
Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2005.
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
| Published: |
Massachusetts Institute of Technology
2006
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/1721.1/32346 |
| _version_ | 1811084505136496640 |
|---|---|
| author | Prince, Robin Neely |
| author2 | Douglas A. Lauffenburger and Richard T. Lee. |
| author_facet | Douglas A. Lauffenburger and Richard T. Lee. Prince, Robin Neely |
| author_sort | Prince, Robin Neely |
| collection | MIT |
| description | Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2005. |
| first_indexed | 2024-09-23T12:51:49Z |
| format | Thesis |
| id | mit-1721.1/32346 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T12:51:49Z |
| publishDate | 2006 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/323462019-04-12T14:58:29Z Localized HB-EGF signaling and Connexin43 decrease in the myocardium Localized heparin-binding epidermal growth factor signaling and Cx43 decrease in the myocardium Prince, Robin Neely Douglas A. Lauffenburger and Richard T. Lee. Massachusetts Institute of Technology. Dept. of Mechanical Engineering. Massachusetts Institute of Technology. Dept. of Mechanical Engineering. Mechanical Engineering. Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2005. Vita. Includes bibliographical references (p. 45-48). Growth factor signaling can affect tissue remodeling through autocrine and paracrine mechanisms. Recent evidence indicates that hypertrophic signaling in cardiomyocytes is induced through transactivation of the epidermal growth factor (EGF) receptor by heparin-binding EGF (HB-EGF). Here it is shown that HB-EGF operates in a spatially restricted local circuit in the extracellular space within the myocardium, revealing the critical nature of the local microenvironment in intercellular signaling. In vitro studies demonstrated that HB-EGF acts as an autocrine growth factor in cultures of rat neonatal cardiomyocytes. However, in vivo experiments in adult mouse left ventricles demonstrated that HB-EGF secretion by a given cardiomyocyte leads to cellular hypertrophy in cells overexpressing HB-EGF and in adjacent cells, but not in cells farther away. This highly localized microenvironment of HB-EGF signaling was also demonstrated using 3D morphology to assess cardiomyocyte growth and was predicted by a computational model of HB- EGF diffusion and binding in the myocardium. Additionally, in vitro and in vivo studies demonstrated that HB-EGF promotes loss of the principal ventricular gap junction protein Connexin43 (Cx43) in cardiomyocytes. Thus, HB-EGF acts as an autocrine and local paracrine cardiac growth factor that leads to loss of gap junction proteins within a spatially confined microenvironment within the myocardium. This demonstration of localized intercellular signaling demonstrates how cells can coordinate remodeling with their immediate neighboring cells without affecting others nearby. by Robin Neely Prince. S.M. 2006-03-29T18:36:12Z 2006-03-29T18:36:12Z 2005 2005 Thesis http://hdl.handle.net/1721.1/32346 61493396 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 56 p. 3286152 bytes 3287316 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology |
| spellingShingle | Mechanical Engineering. Prince, Robin Neely Localized HB-EGF signaling and Connexin43 decrease in the myocardium |
| title | Localized HB-EGF signaling and Connexin43 decrease in the myocardium |
| title_full | Localized HB-EGF signaling and Connexin43 decrease in the myocardium |
| title_fullStr | Localized HB-EGF signaling and Connexin43 decrease in the myocardium |
| title_full_unstemmed | Localized HB-EGF signaling and Connexin43 decrease in the myocardium |
| title_short | Localized HB-EGF signaling and Connexin43 decrease in the myocardium |
| title_sort | localized hb egf signaling and connexin43 decrease in the myocardium |
| topic | Mechanical Engineering. |
| url | http://hdl.handle.net/1721.1/32346 |
| work_keys_str_mv | AT princerobinneely localizedhbegfsignalingandconnexin43decreaseinthemyocardium AT princerobinneely localizedheparinbindingepidermalgrowthfactorsignalingandcx43decreaseinthemyocardium |