RESUMEN
BACKGROUND: Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated. METHODS: CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice. RESULTS: The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice. CONCLUSIONS: ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.
Asunto(s)
Biomarcadores , Riñón , Leucocitos Mononucleares , Proteínas Serina-Treonina Quinasas , Insuficiencia Renal Crónica , Animales , Masculino , Ratones , Biomarcadores/metabolismo , Biomarcadores/sangre , Modelos Animales de Enfermedad , Fibrosis , Riñón/patología , Riñón/metabolismo , Leucocitos Mononucleares/metabolismo , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/sangre , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
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Asunto(s)
Humanos , Masculino , Adulto , Síndrome de Cascanueces Renal/complicaciones , Membrana Basal/fisiopatología , Hematuria/etiología , Anemia/etiología , Proteinuria/etiologíaRESUMEN
Los feocromocitomas y paragangliomas son tumores derivados de células de la cresta neural, que pueden ser diagnosticados mediante la determinación bioquímica de metanefrinas y metoxitiramina. Los avances en la investigación genética han permitido identificar múltiples genes implicados en la fisiopatogenia de estos tumores, de forma que hasta el 35-45% podrían tener una mutación germinal subyacente. Estos genes tienen una firma biológica de transcripción característica y se pueden agrupar en 2 grandes grupos (o clusters), el grupo 1 (VHL y SHDx), con implicación de la vía de la angiogénesis e hipoxia; y el grupo 2 (MEN2 y NF1), implicados en la vía de señalización de la cinasa. A su vez estos genes se asocian a un fenotipo bioquímico (adrenérgicos y noradrenérgicos), y presentación clínica (localización, comportamiento biológico, edad de presentación ) característicos en un número elevado de casos. Un diagnóstico precoz de estos tumores, acompañado de un correcto diagnóstico genético, debe ser una prioridad que permita un mejor tratamiento, la detección precoz de complicaciones, un correctoscreening de familiares y de otros tumores relacionados, así como una mejoría en el pronóstico global de estos pacientes (AU)
Pheochromocytomas and paragangliomas are tumours derived from neural crest cells, which can be diagnosed by biochemical measurement of metanephrine and methoxytyramine. Advances in genetic research have identified many genes involved in the pathogenesis of these tumours, suggesting that up to 35-45% may have an underlying germline mutation. These genes have a singular transcriptional signature and can be grouped into 2 clusters (or groups): cluster 1 (VHL and SHDx), involved in angiogenesis and hypoxia pathways; and cluster 2 (MEN2 and NF1), linked to the kinase signalling pathway. In turn, these genes are associated with a characteristic biochemical phenotype (noradrenergic and adrenergic), and clinical features (location, biological behaviour, age of presentation, etc.) in a large number of cases. Early diagnosis of these tumours, accompanied by a correct genetic diagnosis, should eventually become a priority to enable better treatment, early detection of complications, proper screening of family members and related tumours, as well as an improvement in the overall prognosis of these patients (AU)
Asunto(s)
Humanos , Feocromocitoma/diagnóstico , Paraganglioma/diagnóstico , Detección Precoz del Cáncer , Biomarcadores de Tumor/análisis , Marcadores Genéticos , Técnicas GenéticasRESUMEN
Pheochromocytomas and paragangliomas are tumours derived from neural crest cells, which can be diagnosed by biochemical measurement of metanephrine and methoxytyramine. Advances in genetic research have identified many genes involved in the pathogenesis of these tumours, suggesting that up to 35-45% may have an underlying germline mutation. These genes have a singular transcriptional signature and can be grouped into 2 clusters (or groups): cluster 1 (VHL and SHDx), involved in angiogenesis and hypoxia pathways; and cluster 2 (MEN2 and NF1), linked to the kinase signalling pathway. In turn, these genes are associated with a characteristic biochemical phenotype (noradrenergic and adrenergic), and clinical features (location, biological behaviour, age of presentation, etc.) in a large number of cases. Early diagnosis of these tumours, accompanied by a correct genetic diagnosis, should eventually become a priority to enable better treatment, early detection of complications, proper screening of family members and related tumours, as well as an improvement in the overall prognosis of these patients.
Asunto(s)
Paraganglioma/diagnóstico , Paraganglioma/genética , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Humanos , Neurofibromina 1/genética , Pronóstico , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret/genética , Transducción de Señal , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genéticaRESUMEN
No disponible