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Increased expression of PDGF-B (c-sis) mRNA in rat lung precedes DNA synthesis and tissue repair during chronic hyperoxia.

Authors: Fabisiak, JP  Evans, JN  Kelley, J 
Citation: Fabisiak JP, etal., Am J Respir Cell Mol Biol. 1989 Sep;1(3):181-9.
Pubmed: (View Article at PubMed) PMID:2696512
DOI: Full-text: DOI:10.1165/ajrcmb/1.3.181

Several aspects of tissue response to injury, including cell proliferation, cell migration, and deposition of extracellular matrix, have been attributed to platelet-derived growth factor (PDGF)-like cytokines. Because these responses play key roles in lung injury, PDGF-B (c-sis) gene expression was measured by Northern blot analysis of lung total RNA prepared after oxidant injury was induced by chronic exposure of rats to 85% oxygen for zero, 1, 3, and 7 days. Constitutive but low levels of PDGF-B mRNA (4.0 kb) were observed in the lungs of control animals exposed to 21% oxygen. Steady-state levels of PDGF-B mRNA in lung were elevated 2.5-fold by day 3 of hyperoxia and remained so up to at least day 7. The early increase in PDGF-B mRNA expression after 3 days of hyperoxic exposure preceded several other aspects of the reparative response. DNA synthesis measured by in vivo incorporation of [3H]thymidine into lung DNA was unchanged at day 3 but markedly elevated by day 7. A similar increase in extractable lung RNA implies a quantitative or qualitative change in extractable RNA at this later phase of tissue injury. Subtle changes in actin mRNA expression were also noted late in the course of lung injury. The content of cytoplasmic (beta,gamma) actin mRNA (2.1 kb) in lung was doubled after 7 days of hyperoxia (P less than 0.05). In addition, increased expression of an actin cDNA-hybridizing mRNA, which co-migrates with muscle-specific alpha-actin mRNA (1.7 kb), was detected on day 7, suggesting hyperplasia of smooth muscle and myofibroblasts. These data show that PDGF-B transcripts are constitutively expressed in rat lung tissue. The expression of PDGF-B mRNA increases early in the course of hyperoxic lung injury and precedes an increase in DNA synthesis and other responses that reflect tissue remodeling. These results suggest that the production of PDGF-like cytokines by cells within the lung itself initiates or modulates various aspects of lung injury and repair.

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CRRD ID: 10449500
Created: 2016-01-07
Species: All species
Last Modified: 2016-01-07
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.