Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients

International Journal of Molecular Sciences

Carlos Llorens¹  Pilar Sandoval²  Manuel López-Cabrera²  JoséA Jiménez-Heffernan³  Ricardo Ramos-Ruíz⁴  RaulR. Rodrigues-Diez⁵  Marta Ruiz-Ortega⁵  Rafael Selgas⁶  MaríaA. Bajo⁶  Gloriadel del Peso⁶  Raquel Díaz⁶  Gustavo Laham⁷  Mabel Alvarez-Quiroga⁷ 

[1] BiotechVana S.L. Parc Cientific, 46980 Valencia, Spain;Centro de Biología Molecular “Severo Ochoa” (CBM), Spanish Council for Scientific Research (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain;Departamento de Anatomía Patológica, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario La Princesa, 28006 Madrid, Spain;Fundación Parque Científico de Madrid, Genomics Unit, 28049 Madrid, Spain;Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III, 28029 Madrid, Spain;Research Institute of La Paz (IdiPAZ), University Hospital La Paz, 28046 Madrid, Spain;Sección Nefrología del Centro de Educación Médica e Investigaciones Clínicas (CEMIC), C1431FWO Buenos Aires, Argentina;

关键词: miRNAs;    peritoneal dialysis;    hyalinizing vasculopathy;    peritoneum;    kidney;    endothelial-to-mesenchymal transition;   

DOI  :  10.3390/ijms21165824

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown