Biosynthesized matrix provides a key role for survival signaling in bronchial epithelial cells.
The extracellular matrix (ECM) influences a variety of cellular functions, including survival, adhesion molecule expression, differentiation, and migration. The ECM composition of the epithelial basement membrane is altered in asthmatics. In this study, we elucidate the major survival signals received by bronchial epithelial cells in vitro by studying the effects of a variety of ECM factors and soluble growth factors on bronchial epithelial cell survival. Our findings indicate that the insulin family of soluble growth factors provides important survival signals but also that adhesion to ECM is a crucial determinant of bronchial epithelial cell survival. In the BEAS-2B bronchial epithelial cell line, collagens I and IV, laminin, fibronectin, and vitronectin provide significant levels of protection from apoptosis. Tenascin-C has no effect, whereas elastin and collagen V increase apoptosis to above control levels. BEAS-2B cells secrete their own biosynthesized matrix (BSM), which also provides rescue from apoptosis. Protection by collagen I, fibronectin, and vitronectin was found to be via an RGD domain. Laminin-, collagen IV-, and BSM-mediated survival is not RGD dependent. Primary bronchial epithelial cells exhibit a similar pattern of apoptosis rescue to the BEAS-2B cell line, although we did not observe any vitronectin-mediated protection in the primary cells. These data indicate that bronchial epithelial cell survival is dependent both on soluble growth factors and on a variety of ECM-derived signals.
Wadsworth
Sam J
SJ
Division of Therapeutics and Molecular Medicine, South Block, D Floor, University Hospital, Nottingham NG7 2UH, United Kingdom. Ian.Hall@nottingham.ac.uk
Freyer
Anette M
AM
Corteling
Randolph L
RL
Hall
Ian P
IP
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001485:Basement Membrane / Q000502:physiology; D001798:Blood Proteins / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D020545:Respiratory Mucosa / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012995:Solubility
D001798:Blood Proteins; D016326:Extracellular Matrix Proteins; D006133:Growth Substances