Assuntos
Colestadienóis/metabolismo , Condrodisplasia Punctata/genética , Esteroide Isomerases/genética , Substituição de Aminoácidos , Colestadienóis/sangue , Condrodisplasia Punctata/sangue , Condrodisplasia Punctata/metabolismo , Feminino , Humanos , Recém-Nascido , Modelos Moleculares , Mutação de Sentido Incorreto , Esteroide Isomerases/químicaRESUMO
Although estrogens possess neuroprotective and epileptogenic properties, the expression pattern of the estrogen receptor (ER) following status epilepticus (SE) remains unclear. We therefore examined the expression pattern of ER alpha in the adult rat hippocampus after SE. SE was induced in rats by kainic acid (KA; 12 mg/kg, i.p.). ER alpha expression was assessed by immunostaining and Western blotting at various times (24 h, and 7, 14, and 21 days) after SE onset. Immunohistochemistry disclosed ER alpha expression in the CA1 and CA3 pyramidal cells of control rats, whereas, after SE, ER alpha-immunoreactive neurons decreased in number due to neuronal death in the CA1 from days 7 to 21. On the other hand, ER alpha-immunoreactive cells with astrocytic morphology were observed in the CA1 beginning on day 7 after SE. This immunoreactivity increased in proportion to the hypertrophy of astrocytes up to day 21. Western blotting revealed a significant decrease in ER alpha expression on day 7 after SE in comparison with control level. However, ER alpha expression on days 14 and 21 were similar when comparing KA-treated and control rats. These results indicate that reactive astrocytes are important sites of estrogen action in the hippocampal CA1 after SE.
Assuntos
Receptor alfa de Estrogênio/metabolismo , Regulação da Expressão Gênica/fisiologia , Hipocampo/fisiopatologia , Ácido Caínico , Estado Epiléptico/patologia , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Ratos , Ratos Wistar , Estado Epiléptico/induzido quimicamente , Fatores de TempoRESUMO
Lung injury alters the expression and release of growth factors that disrupt postnatal pulmonary development in newborns and causes chronic lung disease (CLD). The effect of these factors, released into the airways of newborns with CLD, on cell proliferation and collagen production was characterized in vitro. Human fetal lung fibroblast and alveolar-epithelial-like cell lines (FHs 738Lu and A549, respectively) were exposed to tracheal effluents from infants with CLD (mean gestation, 24.7 +/- 0.9 wk; birth weight, 666 +/- 85 g; postnatal age, 0-62 d). In both cell types, proliferation was assessed by measuring [(3)H]-thymidine uptake; in fibroblasts, collagen production was analyzed by measuring [(3)H]-proline incorporation. The activity of specific growth factors in effluents was determined using anti-growth factor antibodies and the growth factors themselves. Growth factors in tracheal effluents promoted proliferation in a dose-dependent manner and caused up to a 10.2- and 3.1-fold increase in thymidine uptake by fibroblasts and epithelial cells, respectively. Collagen production by fibroblasts increased dose dependently, peaking at 177% of baseline. Antibody against transforming growth factor beta-1 (TGF-beta(1)) inhibited proliferation and the increase in collagen production by 31% (p = 0.01) and 14% (p = 0.045), respectively. Antibody against hepatocyte growth factor (HGF) inhibited proliferation of epithelial cells (25%, p = 0.039). The effects of exogenous TGF-beta(1) on fibroblasts and HGF on epithelial cells resembled those of tracheal effluents. Potent mitogenic and differentiating substances are released into the tracheal effluents of newborns with CLD. TGF-beta(1) may worsen CLD by inducing fibrosis whereas HGF may favor resolution by promoting epithelialization.