Increased mir-7641 levels in peritoneal hyalinizing vasculopathy in long-term peritoneal dialysis patients
Entidad
UAM. Departamento de Anatomía Patológica; UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD); Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ); Centro de Biología Molecular Severo Ochoa (CBMSO)Editor
MDPI, Basel, SMwitzerlandFecha de edición
2020-08-13Cita
10.3390/ijms21165824
International Journal of Molecular Sciences 21.16 (2020): 5824
ISSN
1661-6596; 1661-6596 (online)DOI
10.3390/ijms21165824Financiado por
Funding: This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI15/00120 to R.S, PI18/00882 to M.A.B, PI17/00119 to M.R.-O. and Red de Investigación Renal (REDINREN): RD16/0009, to R.S and M.R-O); “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O.); IMPROVE-PD project (“Identification and Management of Patients at Risk–Outcome and Vascular Events in Peritoneal Dialysis”) funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 812699 to M.R.-O. and M.L-C. Spanish Ministry of Science and Innovation/Fondo Europeo de Desarrollo Regional (MICINN/FEDER) (PID2019-110132RB-I00) to M.L.-C.Proyecto
Gobierno de España. PI15/00120; Gobierno de España. PI18/00882; Gobierno de España. PI17/00119; Gobierno de España. RD16/0009; Gobierno de España. EIN2019-103294; info:eu-repo/grantAgreement/EC/H2020/812699/EU//MSC; Gobierno de España. PID2019-110132RB-I00Versión del editor
http://doi.org/10.3390/ijms21165824Materias
Endothelial-to-mesenchymal transition; Hyalinizing vasculopathy; Kidney; MiRNAs; Peritoneal dialysis; Peritoneum; MedicinaDerechos
© 2020 The AuthorsResumen
Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-β1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.
Lista de ficheros
Google Scholar:Díaz, Raquel
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Sandoval, Pilar
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Rodrigues-Diez, Raul R.
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Peso, Gloria Del
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Jiménez Heffernan, José Antonio
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Ramos-Ruíz, Ricardo
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Llorens, Carlos
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Laham, Gustavo
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Alvarez-Quiroga, Mabel
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López-Cabrera, Manuel
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Ruiz Ortega, Marta
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Bajo Rubio, María Auxiliadora
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Selgas, Rafael
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