RESUMEN
Chromogranin A (CgA), originally identified in adrenal chromaffin cells, is a member of the granin family of acidic secretory glycoproteins that are expressed in endocrine cells and neurons. CgA has been proposed to play multiple roles in the secretory process. Intracellularly, CgA may control secretory granule biogenesis and target neurotransmitters and peptide hormones to granules of the regulated pathway. Extracellularly, peptides formed as a result of proteolytic processing of CgA may regulate hormone secretion. To investigate the role of CgA in the whole animal, we created a mouse mutant null for the Chga gene. These mice are viable and fertile and have no obvious developmental abnormalities, and their neural and endocrine functions are not grossly impaired. Their adrenal glands were structurally unremarkable, and morphometric analyses of chromaffin cells showed vesicle size and number to be normal. However, the excretion of epinephrine, norepinephrine, and dopamine was significantly elevated in the Chga null mutants. Adrenal medullary mRNA and protein levels of other dense-core secretory granule proteins including chromogranin B, and secretogranins II to VI were up-regulated 2- to 3-fold in the Chga null mutant mice. Hence, the increased expression of the other granin family members is likely to compensate for the Chga deficiency.
Asunto(s)
Cromograninas/genética , Cromograninas/fisiología , Marcación de Gen , Sistemas Neurosecretores/fisiología , Vesículas Secretoras/fisiología , Médula Suprarrenal/metabolismo , Animales , Catecolaminas/orina , Cromogranina A , Femenino , Eliminación de Gen , Expresión Génica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Sistemas Neurosecretores/metabolismo , Regulación hacia ArribaAsunto(s)
Embolización Terapéutica , Hemorragia/cirugía , Úlcera/complicaciones , Anciano , Femenino , HumanosRESUMEN
Small bowel neoplastic disease is a rare but dreaded occurrence in Crohn's disease (CD) and the diagnosis is often disguised by nonspecific and varied presenting symptoms mimicking active or obstructive CD. As such, the diagnosis is all too often delayed, typically detected at a late stage, and with a poor prognosis. CD has become a well-recognized risk factor for the development of small bowel adenocarcinoma. The data, however, are limited and based on case reports, retrospective studies, and review of the literature.