Heparin inhibits DNA synthesis and gene expression in alveolar type II cells.
Responses of isolated type II alveolar cells to fibroblast growth factors (FGF) have been shown to be sensitive to the level of sulfation in extracellular matrix (ECM) substrata. These observations may reflect the specific in situ distribution and level of sulfation of ECM within the alveolar basement membranes (ABM) associated with type II cells. The goal of this study was to determine if the model sulfated ECM heparin modified DNA synthesis and gene expression by type II cells in a concentration dependent-manner. Isolated rat type II cells were exposed to different concentrations of heparin (0.005-500 micro g/ml) in serum-free medium for 1-3 d with or without FGF-1 or FGF-2. The effects of heparin were examined by [(3)H]thymidine incorporation into DNA, total cell protein, cell number, and selected gene expression. Results indicated that heparin inhibited [(3)H]thymidine uptake in a concentration-dependent manner. Total protein, cell number, and FGF-2 protein expression and mRNA of FGF-1, -2, and FGF receptor-2 detected by reverse transcriptase-polymerase chain reaction were decreased by heparin. These results demonstrate that sulfated molecules in the ABM may play important regulatory role(s) in selected type II cell activities during normal cell homeostasis, turnover, and repair after lung injury.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
Cheng-Ming
CM
Li
Donna
D
Newman
Jody
J
Khosla
Philip L
PL
Sannes
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000235:genetics; D013936:Thymidine / Q000378:metabolism
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D004247:DNA; C496350:Fgfr1 protein, rat; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D013936:Thymidine