Mechanical strain-induced posttranscriptional regulation of fibronectin production in fetal lung cells.
We have shown that intermittent mechanical strain, simulating fetal breathing movements, stimulated fetal rat lung cell proliferation. Because normal lung growth requires proper coordination between cell proliferation and extracellular matrix remodeling, we investigated the effect of strain on fibronectin metabolism. Organotypic cultures of fetal rat lung cells, subjected to intermittent strain, showed increased fibronectin content in the culture media. Fibronectin-degrading activity in media from strained cells was similar to that of static cultures. Northern analysis revealed that strain inhibited fibronectin mRNA accumulation seen during static culture. Synthesis of fibronectin, determined by metabolic labeling, was increased by strain despite lower mRNA levels or presence of actinomycin D. This increase was not mediated via a rapamycin-sensitive mechanism. Strain stimulated prelabeled fibronectin secretion even in the presence of cycloheximide. These results suggest that strain differentially regulates fibronectin production of fetal lung cells at the transcriptional and posttranscriptional levels. Mechanical strain increases soluble fibronectin content by stimulating its synthesis and secretion without increasing fibronectin message levels.
Thoracic Surgery Research Laboratory, Toronto General Hospital Research Institute, The Medical Research Council Group in Lung Development, University of Toronto, Toronto, Ontario, Canada M5G 2C4.
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Mourgeon
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Xu
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Tanswell
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Liu
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Post
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000196:embryology*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats / Q000196:embryology; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D012995:Solubility; D013314:Stress, Mechanical
D004791:Enzyme Inhibitors; D005353:Fibronectins; D012333:RNA, Messenger; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus