TGF-beta1 and fibroblast growth factor-1 modify fibroblast growth factor-2 production in type II cells.
Fibroblast growth factor (FGF)-2, which stimulates DNA synthesis by type II cells in the lung, has been shown to be regulated by transforming growth factor (TGF)-beta1, an important inflammatory cytokine, in vascular epithelium. The goal of this study was to determine if FGF-2 production by alveolar type II cells is modulated by TGF-beta1 or FGF-1, which also stimulates DNA synthesis by type II cells. Isolated rat type II cells were exposed to 0-40 ng/ml of TGF-beta1 or 0-500 ng/ml of FGF-1 in serum-free medium for 1-5 days. With a specific immunoassay, significant increases of FGF-2 protein in type II cell lysates to levels above those in control cells were achieved after 1 day of exposure to 100 ng/ml of FGF-1 and after 3 days of treatment with 8 ng/ml of TGF-beta1. Similarly, transcripts for FGF-2 were dramatically increased above those in control cells with TGF-beta1 or FGF-1, as were those for FGF receptor-1. These results demonstrate important regulatory links between FGF-2 and both TGF-beta1 and FGF-1 in the alveolar epithelium that could contribute to the regulation of normal cell turnover, development, and the repair processes after injury in the lung.
Li
C M
CM
Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
Khosla
J
J
Pagan
I
I
Hoyle
P
P
Sannes
P L
PL
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1