β1-integrin∕FAK Initiated MAPK/ERK Pathway Regulates Human Fetal Islet Cell Development and Survival
Date of Award
2006
Degree Type
Thesis
Degree Name
Master of Science
Program
Physiology and Pharmacology
Supervisor
Dr. Rennian Wang
Second Advisor
Dr. Stephen Sims
Third Advisor
Dr. Geoff Pickering
Abstract
βl integrin and collagen matrix interactions regulate cell survival by associating with FAK and initiating MAPK/ERK signaling, but little is known about these pathways during human fetal islet ontogeny. This study investigated whether βl integrin/FAK activation of the MAPK/ERK pathway is involved in regulating human fetal islet cell survival and expression of endocrine cell markers. Isolated human fetal islet-epithelial cell clusters pre-treated with an anti-βl integrin antibody and cultured on type I collagen showed decreased cell spreading and increased cell death. Blockade of βl integrin induced a disorganization of focal adhesion contacts in the cell clusters and decreased activation of FAK and ERK1/2 leading to a reduction in PDX-1, insulin and glucagon- expressing cells, βl integrin siRNA yielded similar results. Activation of FAK increased ERK1/2 phosphorylation, as well as insulin and glucagon gene/protein expression. This study demonstrates that activation of FAK/MAPK/ERK signaling by βl integrin is required for the differentiation and survival of human fetal islet cells.
Recommended Citation
Saleem, Saira, "β1-integrin∕FAK Initiated MAPK/ERK Pathway Regulates Human Fetal Islet Cell Development and Survival" (2006). Digitized Theses. 4683.
https://ir.lib.uwo.ca/digitizedtheses/4683