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Biomedical subjects

K M Sterling

Publications and source records attributed to K M Sterling.

8 recordsLinked to original sources
PubMed1987

Regulation of types I, III, and IV procollagen mRNA synthesis in glucocorticoid-mediated intestinal development.

Administration of dexamethasone (0.8 mg/kg) to 9-day-old rats once daily for 3 consecutive days caused precocious induction of adult specific disaccharidase activity in the small intestine. Maturation-specific disaccharidase activity was accompanied by decreased amounts of types I and III collagen and decreased procollagen type I and III mRNA levels. Conversely, type IV procollagen, fibronectin, and laminin amounts and their respective mRNA levels were increased. In vitro transcription of nuclei isolated from small intestine and colon of suckling rats indicated a decreased rate of synthesis of procollagen types I and III mRNAs and an increased rate of synthesis of procollagen type IV mRNAs and laminin mRNAs after dexamethasone treatment. The data suggest that glucocorticoids mediate a differential regulation of interstitial and basement membrane collagen gene expression in the developing rat intestine.

Animals↗
PubMed1986

Glucocorticoids decrease the synthesis of type I procollagen mRNAs.

Glucocorticoids selectively decrease procollagen synthesis in animal and human skin fibroblasts. beta-Actin content and beta-actin mRNA are not affected by glucocorticoid treatment of chick skin fibroblasts. The inhibitory effect of glucocorticoids on procollagen synthesis is associated with a decrease in total cellular type I procollagen mRNAs in chick skin fibroblasts. These effects of dexamethasone are receptor mediated as determined by pretreatment with the glucocorticoid antagonists progesterone and RU-486 and with the agonist beta-dihydrocortisol. Dexamethasone has a small but significant inhibitory effect on cell growth of chick skin fibroblasts. The ability of this corticosteroid to decrease the steady-state levels of type I procollagen mRNAs in nuclei, cytoplasm, and polysomes varies. The largest decrease of type I procollagen mRNAs is observed in the nuclear and cytoplasmic subcellular fractions 24 h after dexamethasone treatment. Type I procollagen hnRNAs are also decreased as determined by Northern blot analysis of total nuclear RNA. The synthesis of total cellular type I procollagen mRNAs is reversibly decreased by dexamethasone treatment. In addition the synthesis of total nuclear type I procollagen mRNA sequences is decreased at 2, 4, and 24 h following the addition of radioactive nucleoside and dexamethasone to cell cultures. Although the synthesis of pro alpha 1(I) and pro alpha 2(I) mRNAs is decreased in dexamethasone-treated chick skin fibroblasts, the degradation of the total cellular procollagen mRNAs is not altered while the degradation of total cellular RNA is stabilized. These data indicate that the dexamethasone-mediated decrease of procollagen synthesis in embryonic chick skin fibroblasts results from the regulation of procollagen gene expression.

Actins↗
PubMed1983

Bleomycin treatment of chick fibroblasts causes an increase of polysomal type I procollagen mRNAs. Reversal of the bleomycin effect by dexamethasone.

Bleomycin treatment of primary chick skin fibroblasts and chick lung fibroblasts resulted in a selective dose-dependent increase of cell layer procollagen synthesis. Solid support hybridization of total cellular RNA to 32P-labeled pro-alpha 1(I) and pro-alpha 2(I) cDNAs did not indicate an increase of total cellular procollagen type I mRNAs in bleomycin-treated cells. However, bleomycin treatment of chick skin fibroblasts causes a redistribution of procollagen type I mRNAs within the nuclear, cytoplasmic, and polysomal subcellular fractions. Both the nuclear and cytoplasmic procollagen type I mRNAs are significantly decreased in concentration after bleomycin administration. In contrast, the polysomal procollagen type I mRNAs are significantly increased in both chick skin and lung fibroblasts treated with bleomycin. Administration of dexamethasone to bleomycin-treated fibroblasts resulted in a reversal of the bleomycin-induced increase in cell layer procollagen synthesis. The increased amounts of polysomal procollagen type I mRNAs in bleomycin-treated cells were also reduced by subsequent administration of dexamethasone. These data indicate that bleomycin treatment of chick skin and chick lung fibroblasts results in a specific increase in procollagen synthesis in the cell layer which is mediated by elevated levels of polysomal type I procollagen mRNAs via a repartitioning of these mRNAs within the fibroblast. Furthermore, dexamethasone reverses the bleomycin-induced elevations of both cell layer procollagen synthesis and polysomal type I procollagen mRNAs.

Animals↗
PubMed1983

Dexamethasone decreases the amounts of type I procollagen mRNAs in vivo and in fibroblast cell cultures.

Dexamethasone treatment of neonatal chicks resulted in a time- and dose-dependent selective decrease of skin collagen synthesis. Total RNA of chick skin was isolated and hybridized to the cloned cDNAs pCg54 for pro-alpha 1 (I) mRNA and pCg45 for pro-alpha 2(I) mRNA. RNA isolated from the total skin of chicks receiving various doses of dexamethasone had dose-related decreases of pro-alpha 1 (I) and pro-alpha 2(I) mRNAs. The decrease of type I procollagen mRNAs for various doses of dexamethasone were similar to the decreases observed for collagen synthesis in vivo. Dexamethasone treatment of chick skin and chick lung fibroblasts resulted in a selective decrease of procollagen synthesis. A dose-related decrease of procollagen synthesis was observed with chick skin fibroblasts. Dexamethasone-treated chick skin and chick lung fibroblasts had decreased levels of pro-alpha 1 (I) and pro-alpha 2(I) mRNAs as determined by solid support hybridization with pCg54 and pCg45. The dexamethasone-mediated decreases of type I procollagen mRNAs in skin fibroblasts and lung fibroblasts were similar to the decreases observed in procollagen synthesis.

Animals↗
PubMed1982

Inhibition of collagen accumulation by glucocorticoids in rat lung after intratracheal bleomycin instillation.

Male Fischer 344 rats were given a single lung instillation of bleomycin sulfate (0.6 units/100 g). some animals were treated 24 hr after bleomycin administration with triamcinolone diacetate. Steroid treatment was continued on alternate days for 4 weeks. At the end of 4 weeks, the lungs of rats receiving bleomycin alone had two-fold increases of both prolyl hydroxylase activity and proteinaceous hydroxyproline as compared to control values. The lungs of bleomycin-treated rats which received 4 mg of triamcinolone diacetate per kg on alternate days had a 33% increase of prolyl hydroxylase activity and proteinaceous hydroxyproline content of bleomycin-treated animals receiving glucocorticoid (8 mg/kg) on alternate days were the same as control values. The results indicate that alternate day administration of the synthetic glucocorticoid triamcinolone diacetate blocks lung collagen accumulation following a single intratracheal dose of bleomycin to rats.

Animals↗
PubMed1982

Bleomycin-induced increase of collagen turnover in IMR-90 fibroblasts: an in vitro model of connective tissue restructuring during lung fibrosis.

Late-log-phase IMR-90 human fetal lung fibroblasts were incubated with bleomycin sulfate for 48 hr. The culture medium was removed and replaced with serum-free medium and [5-3H]proline. The cells were then incubated for increasing time intervals. The cells and culture medium were collected, and radioactive proline incorporated into collagen and noncollagen protein was determined. Intracellular collagen synthesis was selectively increased. Furthermore, polysomes isolated from bleomycin-treated cells synthesized significantly more collagen in the wheat germ lysate than did control polysomes. Prolyl hydroxylase activity was also increased significantly in the bleomycin-treated cells. Free and peptide-bound radioactive hydroxyproline in the cells and medium was greatly increased in bleomycin-treated cells, which indicates increased collagen degradation. The results demonstrate that, although collagen synthesis in lung fibroblasts is increased by bleomycin, the newly synthesized collagen is rapidly degraded in both the cell layer and the medium. This increased collagen degradation may be responsible for the remodeling which takes place during lung fibrosis.

Bleomycin↗
PubMed1981

Collagen lysyl oxidase activity in the lung increases during bleomycin-induced lung fibrosis.

Intratracheal administration of bleomycin caused pulmonary fibrosis in rats. Bleomycin sulfate (640 micro grams/165 g b.wt. in 0.5 ml of sterile saline) was instilled Intratracheally into male Fisher 344 rats (169 +/- 5 g), whereas control animals received 0.5 ml of sterile saline by the same route. One, 3, 7, 14, 28 and 322 days after instillation, the animals were killed, the lungs were homogenized in 6 M urea, 0.01 M NaCl, 0.001 M potassium phosphate (pH 8.3) and the homogenates were subjected to ultracentrifugation. The 106,000 x g supernate was assayed for lysyl oxidase activity. Total lung hydroxyproline and desmosine content was determined at each time point. Lysyl oxidase specific activity in the lung was elevated significantly 3 days after bleomycin treatment, peaked 14 days after bleomycin treatment at 230% above the control value and was returned toward normal 28 days after treatment. The increase of lysyl oxidase activity preceded the maximal increase of total lung hydroxyproline and desmosine which occurred 28 days after bleomycin instillation.

Amino Acid Oxidoreductases↗