Ontogeny and regulation of platelet-derived growth factor gene expression in distal fetal rat lung epithelial cells.
Using flow cytometry, thymidine uptake into DNA, and expression of two growth-related genes, histone 3 and c-myc, we found an increase in the proportion of distal lung epithelial cells in the G0/G1 phase of the cell cycle with advancing gestation. Since our previous studies had demonstrated that platelet-derived growth factor (PDGF) is essential for the progression of these cells from the G0/G1 to the S phase of cell cycle, we investigated the gene and protein expression of PDGF-related genes (PDGF-A, PDGF-B, alpha-receptor, and beta-receptor) in distal fetal lung epithelial cells. The cells transcribed all the PDGF-related genes and translated the PDGF-A and PDGF-B mRNAs into protein, as demonstrated by immunocytochemistry and immunoprecipitation. To explore an autocrine role for PDGF in distal fetal lung epithelial cells, intervention studies using PDGF-A and -B chain-specific antisense oligodeoxynucleotides (ODN) were carried out. Antisense PDGF-B ODN, but not antisense PDGF-A ODN, significantly reduced the DNA synthesis of these cells. The inhibitory effect of antisense PDGF-B ODN on DNA synthesis was reversed by the addition of exogenous PDGF-BB, which supports an autocrine role in the DNA synthesis of these cells. We also examined the expression of PDGF genes in distal fetal lung epithelial cells during late gestation. PDGF-A chain and beta-receptor gene expressions declined with advancing gestation, whereas expression of message for PDGF-B chain and alpha-receptor increased. The increases in message for PDGF-B chain and alpha-receptor with advancing gestation were due to a greater rate of transcription, whereas the developmental decrease of PDGF-A chain and beta-receptor mRNAs was caused by a decrease in RNA stability. Taken together with the ODN data, these results suggest that the G0/G1 cell cycle arrest of distal lung epithelial cells during late fetal gestation is due to a decrease in PDGF beta-receptor expression by the cells.[1]References
- Ontogeny and regulation of platelet-derived growth factor gene expression in distal fetal rat lung epithelial cells. Buch, S., Jassal, D., Cannigia, I., Edelson, J., Han, R., Liu, J., Tanswell, K., Post, M. Am. J. Respir. Cell Mol. Biol. (1994) [Pubmed]
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