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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotracheal bleomycin administration in rats and other animal species causes rapid development of pulmonary fibrosis, characterized by increased lung collagen synthesis and deposition. To clarify the mechanism, lung fibroblasts from bleomycin-treated rats (BRF) were isolated and maintained in tissue culture. They were then compared with those from normal untreated control animals, with respect to several key parameters of collagen metabolism. BRF synthesized collagen at a rate 35-82% above normal rat lung fibroblasts (NRF). This difference did not appear to be due to the selection of a clone by the subculture process. Furthermore, analysis of newly synthesized collagen type composition, revealed a significantly lower ratio of type III to type I collagen. Noncollagenous protein synthesis, however, was not significantly different from normal. Collagenase production and growth rate were also unaffected. BRF, however, was morphologically indistinguishable from NRF, even at the ultrastructural level. Upon further bleomycin (1 microgram/ml) exposure in vitro, BRF could be further stimulated to synthesize collagen at 82% above the rate for untreated BRF. This is comparable to the 90% increase in NRF treated in vitro (compared with untreated NRF). These results would favor the conclusion that bleomycin induces pulmonary fibrosis, by causing directly and/or indirectly lung fibroblasts (or a certain line of lung fibroblasts) to synthesize collagen at a higher rate without any associated increase in growth rate. The data, however, do not rule out the possibility that the fibroblast isolation procedure has selected for a certain population of fibroblasts that may not be typical of the in vivo situation.
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PMID:Rat lung fibroblast collagen metabolism in bleomycin-induced pulmonary fibrosis. 241 Apr 57

To clarify the mechanism of pulmonary fibrosis, the growth rate of fibroblasts obtained from bleomycin (BLM)-treated rats was compared with that of fibroblasts obtained from control rats. Proliferation of fibroblasts obtained from rats at 4 days after BLM instillation (BRF) was significantly more rapid than that of fibroblasts obtained from rats at 4 days after saline instillation (CRF), as assessed by cell counting and 3H-TdR incorporation. CRF and BRF were separated by the method of discontinuous Percoll gradients. Three fibroblast fractions of specific gravity (S.G.), S.G. < 1.036, 1.036 < or = S.G. < 1.050, 1.050 < or = S.G. < 1.062, were obtained. Percentages of the densest fibroblast fraction were 46.2 +/- 5.2 in BRF and 6.4 +/- 2.8 in CRF. The densest fibroblasts in BRF proliferated more rapidly than the least dense fibroblasts. Rat rIL-1 alpha suppressed the proliferation of CRF and BRF, dose dependently. These results suggest that an increase in the densest fibroblasts in the lung might correlate with BLM-induced pulmonary fibrosis and that IL-1 alpha suppresses the proliferation of pulmonary fibroblasts.
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PMID:[Proliferation of pulmonary fibroblasts obtained from rats with bleomycin-induced pulmonary fibrosis and effects of rat rIL-1 alpha on this proliferation]. 752 79

Fibroblasts from bleomycin-injured lungs express telomerase activity transiently during the period of active fibrosis, but the signal(s) responsible for its induction is (are) unknown. The objective of this study was to identify potential mediators capable of regulating telomerase activity induction in rat lung fibroblasts during pulmonary fibrosis. Lung fibroblasts from control (NRF) and bleomycin-treated (BRF) rats were isolated and treated in vitro with either basic fibroblast growth factor (bFGF) or interleukin-4 (IL-4). At selected time points after treatment, the cells were analyzed for telomerase activity, as well as telomerase reverse transcriptase (TERT) mRNA and protein by reverse transcriptase/polymerase chain reaction and Western blot, respectively. The results showed that bFGF could induce telomerase activity in NRF and stimulate further the induced activity in BRF. The bFGF effect was accompanied by increased TERT protein expression and a rapid but transient increase in TERT mRNA. In contrast, IL-4 inhibited the induced telomerase activity in BRF, which was accompanied by increased alpha-smooth muscle actin expression, an indicator of myofibroblast differentiation. These findings suggest that telomerase expression could be induced in rat lung fibroblasts by bFGF, but suppressed by IL-4, which promoted myofibroblast differentiation. The latter is consistent with the preferential expression of telomerase activity in fibroblasts relative to myofibroblasts.
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PMID:Regulation of telomerase activity in rat lung fibroblasts. 1197 Sep 2