Molecular responses of rat tracheal epithelial cells to transmembrane pressure.
Smooth muscle constriction in asthma causes the airway to buckle into a rosette pattern, folding the epithelium into deep crevasses. The epithelial cells in these folds are pushed up against each other and thereby experience compressive stresses. To study the epithelial cell response to compressive stress, we subjected primary cultures of rat tracheal epithelial cells to constant elevated pressures on their apical surface (i.e., a transmembrane pressure) and examined changes in the expression of genes that are important for extracellular matrix production and maintenance of smooth muscle activation. Northern blot analysis of RNA extracted from cells subjected to transmembrane pressure showed induction of early growth response-1 (Egr-1), endothelin-1, and transforming growth factor-beta1 in a pressure-dependent and time-dependent manner. Increases in Egr-1 protein were detected by immunohistochemistry. Our results demonstrate that airway epithelial cells respond rapidly to compressive stresses. Potential transduction mechanisms of transmembrane pressure were also investigated.
Ressler
B
B
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA.
Lee
R T
RT
Randell
S H
SH
Drazen
J M
JM
Kamm
R D
RD
D000818:Animals; D015152:Blotting, Northern; D016923:Cell Death; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003720:Densitometry; D051766:Early Growth Response Protein 1; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D008297:Male; D008566:Membranes / Q000502:physiology; D010812:Physical Stimulation; D011312:Pressure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014132:Trachea / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D019332:Endothelin-1; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016212:Transforming Growth Factor beta