Calcyclin gene expression is increased by mechanical strain in fibroblasts and lung.
Mechanical tension extending throughout the structural elements of the lung is a potential stimulus for cell proliferation and gene expression. Pulmonary fibroblasts located in the interstitial space of the capillary wall throughout the lung parenchyma and within the large vessels and airways are uniquely situated to sense changes in mechanical force. Therefore, we used the polymerase chain reaction-based method of differential display analysis to screen for altered gene expression in fetal human lung fibroblasts exposed to increased cyclic stretch. IMR-90 cells were seeded at 3 x 10(4) cells/cm(2) on laminin-coated plates. Cells were subsequently exposed to mechanical strain on a Flexercell apparatus, resulting in a maximal elongation of 20% at a rate of 60 cycles/min over a period of 48 h. A complementary DNA corresponding to the cell cycle-regulated gene calcyclin was identified in mechanically strained fibroblasts. Increased calcyclin messenger RNA levels were confirmed by Northern blot analysis. Further, calcyclin gene expression was upregulated in isolated-perfused rat lungs exposed to increased mechanical strain by ventilation at high states of lung inflation for 4 h. These data suggest that calcyclin gene expression plays a role in the response of pulmonary fibroblasts to increased mechanical tension and may alter the regulation of the fibroblast cell cycle.
Breen
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Division of Physiology, Department of Medicine, University of California, San Diego, USA.
Fu
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Normand
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D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002460:Cell Line; D018076:DNA, Complementary / Q000032:analysis; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D010477:Perfusion; D012123:Pulmonary Ventilation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013314:Stress, Mechanical; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C489132:S100a6 protein, rat; C055351:S100A6 protein, human