RESUMEN
BACKGROUND: International consensus diagnostic criteria (ICDC) have been proposed to classify autoimmune pancreatitis (AIP) in type 1, type 2, or not otherwise specified. OBJECTIVE: Aim was to apply the ICDC to an Italian series of patients to evaluate the incidence and clinical profiles among different subtypes of AIP. METHODS: we re-evaluated and classified 92 patients diagnosed by Verona criteria, according to the ICDC. RESULTS: Out of 92 patients, 59 (64%) were diagnosed as type 1, 17 (18%) as type 2, and 15 (16%) as not otherwise specified according to the ICDC. A significant difference between type 1 and type 2 were found for age (54.5 ± 14.5 vs. 34.4 ± 13.9 respectively; p < 0.0001), male sex (76 vs. 47%; p = 0.007), jaundice (66 vs. 18%; p = 0.002) and acute pancreatitis (9 vs. 47%; p < 0.0001), elevated serum IgG4 levels (85 vs. 7%; p < 0.0001), inflammatory bowel disease (8 vs. 82%; < 0.0001), and relapse of the disease (34 vs. 6%; p = 0.058). Imaging and response to steroids in the not-otherwise-specified group were similar to type 1 and 2. CONCLUSIONS: Type 1 has a different clinical profile from type 2 autoimmune pancreatitis. The not-otherwise-specified group has peculiar clinical features which are shared both with type 1 or type 2 groups.
RESUMEN
TGF-beta1 is a potent inhibitor of growth and DNA synthesis in thyroid cells. It has also been shown that TGF-beta1 inhibits thyrocyte function. The functional inhibition is represented by a downregulation of thyroid specific genes, such as Na(+)/I(-) symporter (NIS), thyroglobulin (TG) and thyroperoxidase (TPO). The transcriptional control of these genes is mediated by thyroid-specific transcription factors: thyroid transcription factor-1 (TTF-1) and PAX-8. It has been shown that Smad proteins play a pivotal role in the intracellular signal transduction of the TGF-beta family members. In this paper, the functional relevance of Smad4, in the control of thyroid differentiation genes and thyroid-specific transcription factors, has been investigated. The data obtained provides, for the first time, evidence that D.N. Smad4-100T is capable of blocking TGF-beta1 action in the regulation of thyroid-specific genes expression. Such action is possible by blocking nuclear translocation of Smad4 and Smad2.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Glándula Tiroides/efectos de los fármacos , Factor de Crecimiento Transformador beta/farmacología , Animales , Autoantígenos/genética , Autoantígenos/fisiología , Northern Blotting , Western Blotting , Línea Celular , Células Clonales , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/fisiología , Regulación hacia Abajo , Regulación de la Expresión Génica/efectos de los fármacos , Vectores Genéticos/genética , Inmunohistoquímica , Yoduro Peroxidasa/genética , Yoduro Peroxidasa/fisiología , Proteínas de Unión a Hierro/genética , Proteínas de Unión a Hierro/fisiología , Luciferasas/genética , Luciferasas/metabolismo , Mutación/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factor de Transcripción PAX8 , Factores de Transcripción Paired Box , Fosforilación , Ratas , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Transducción de Señal/fisiología , Proteína Smad2 , Proteína Smad4 , Simportadores/genética , Simportadores/fisiología , Glándula Tiroides/citología , Factor Nuclear Tiroideo 1 , Tirotropina/farmacología , Transactivadores/genética , Transactivadores/metabolismo , Transactivadores/fisiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transfección , Factor de Crecimiento Transformador beta/fisiología , Factor de Crecimiento Transformador beta1RESUMEN
Transforming growth factor beta 1 (TGF-beta 1) and insulin-like growth factor I (IGF-I) have contrasting effects on cell cycle regulation in thyroid cells and TGF-beta 1 induces a dramatic decrease in IGF-I-induced cell proliferation. The aim of the present study was to investigate the molecular mechanism of cross-talk between TGF-beta 1 and IGF-I in FRTL-5 cells. TGF-beta 1 affected IGF-I-stimulated insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation and its association with Grb2 protein. Moreover, TGF-beta 1 decreased the IGF-I-induced tyrosine phosphorylation of the adaptor protein CrkII and its association with the IGF-I receptor. These results were accompanied by TGF-beta 1 inhibition of IGF-I-stimulated mitogen-activated protein kinase phosphorylation and activation. Conversely, TGF-beta 1 did not alter IGF-I-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity, IGF-I-induced tyrosine phosphorylation of Shc, and its binding to Grb2. Taken together, these findings provide a molecular basis for the growth-inhibitory action of TGF-beta 1 on the IGF-I-induced mitogenic effect.
