Información de la revista
Vol. 39. Núm. 3.Mayo - Junio 2019
Páginas 223-338
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 39. Núm. 3.Mayo - Junio 2019
Páginas 223-338
DOI: 10.1016/j.nefro.2018.12.013
Open Access
New targets for renal and hepatic cystogenesis. The help of proteomic in the understanding of ADPKD
Visitas
83
Marta Vizoso-González1, Adrián Cordido1, Vanesa Calviño-Louzao1, Cándido Díaz2, Susana Bravo3, Miguel A. García-González4
1 Nephrology Laboratory, Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, A Coruña, Spain
2 Nephrology Department, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Santiago de Compostela, A Coruña, Spain
3 Proteomic Unit, Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, A Coruña, Spain
4 Nephrology Laboratory, Instituto de Investigación Sanitaria de Santiago de Compostela - Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, A Coruña, Spain
Este artículo ha recibido
83
Visitas

Under a Creative Commons license
Información del artículo
Texto completo
Descargar PDF
Estadísticas
Texto completo

Introduction: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic disorder characterized by developing fluid-filled cyst derived from the tubule epithelial cells in kidney, and several extrarenal manifestations as hepatic cysts (Polycystic Liver Disease [PLD]). Different mechanisms have been related to the pathogenesis of renal and hepatic cystogenesis. The identification of the main cystogenic pathway has not been found, and effective therapeutic approach to block cystogenesis remains undiscovered.

Method: We have recollected kidney and livers from Pkd1cond/condTamCre mice. This model presents a cystogenesis developmental window, because the inactivation of Pkd1 gene in different points of life determines cystic phenotype. We inactivated Pkd1 at postnatal day 10/11 (cystic window) and postnatal day 15/16 (non-cystic window), which led us to study the differences between wild-type and mutant mice. Finally, we sacrificed them at postnatal day30. Liver and kidney protein were extracted and the proteome was sequenced using mass spectrometry MALDI-TOF. Finally, we used bioinformatics tools to identified the proteins and pathways involved in cystogenesis. By proteomic approaches, we described novel list of proteins implicated in renal and hepatic cystogenesis (up and down regulated), which are likely to be used as therapeutic targets.

Results: We have identified the renal and hepatic proteome of cysts from a good characterized animal model in the ADPKD field, the Pkd1cond/condTamCre mice. After comparing the different samples (kidney and liver), cystic and non-cystic, we have identified a list of proteins directly implicated in the process of cystogenesis. Related to liver, we found 26 proteins that appear only on cystic samples and 8 that not appear. However in kidney, we recognized 16 proteins that appear only on cystics and 6 that not appear on them.

Also, we studied the pathways related to these proteins to enlarge the understanding of molecular basis of renal and hepatic cystogenesis. We found that, in both cases, main altered pathways are immune system, signal transduction, metabolism and metabolism of proteins. Moreover, there are more specific pathways; vesicle-mediated transport and cell cycle in liver, in contrast to developmental biology and extracellular matrix organization in kidney.

Conclusion: Our results described a list of new possible targets which could be used as future and more specific therapeutic approaches for renal and hepatic phenotype of ADPKD. Furthermore, and given that the key factor or pathways of cystogenesis in still unknown, our data helps to a better understanding of molecular basis of the disease.

Idiomas
Nefrología

Suscríbase a la newsletter

Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.