RT Journal Article
T1 Inflammation, Senescence and MicroRNAs in Chronic Kidney Disease.
A1 Carmona, Andres
A1 Guerrero, Fatima
A1 Jimenez, Maria Jose
A1 Ariza, Francisco
A1 Agüera, Marisa L
A1 Obrero, Teresa
A1 Noci, Victoria
A1 Muñoz-Castañeda, Juan Rafael
A1 Rodríguez, Mariano
A1 Soriano, Sagrario
A1 Moreno, Juan Antonio
A1 Martin-Malo, Alejandro
A1 Aljama, Pedro
K1 chronic kidney disease
K1 microRNAs
K1 microvesicles
K1 monocytes CD14+CD16++
K1 vascular smooth muscle cells
AB Patients with chronic kidney disease (CKD) show a chronic microinflammatory state that promotes premature aging of the vascular system. Currently, there is a growth interest in the search of novel biomarkers related to vascular aging to identify CKD patients at risk to develop cardiovascular complications. Forty-five CKD patients were divided into three groups according to CKD-stages [predialysis (CKD4-5), hemodialysis (HD) and kidney transplantation (KT)]. In all these patients, we evaluated the quantitative changes in microRNAs (miRNAs), CD14+C16++ monocytes number, and microvesicles (MV) concentration [both total MV, and monocytes derived MV (CD14+Annexin V+CD16+)]. To understand the molecular mechanism involved in senescence and osteogenic transdifferentation of vascular smooth muscle cells (VSMC), these cells were stimulated with MV isolated from THP-1 monocytes treated with uremic toxins (txMV). A miRNA array was used to investigate serum miRNAs profile in CKD patients. Reduced expression levels of miRNAs-126-3p, -191-5p and -223-3p were observed in CKD4-5 and HD patients as compared to KT. This down-regulation disappeared after KT, even when lower glomerular filtration rates (eGFR) persisted. Moreover, HD patients had higher percentage of proinflammatory monocytes (CD14+CD16++) and MV derived of proinflammatory monocytes (CD14+Annexin V+CD16+) than the other groups. In vitro studies showed increased expression of osteogenic markers (BMP2 and miRNA-223-3p), expression of cyclin D1, β-galactosidase activity and VSMC size in those cells treated with txMV. CKD patients present a specific circulating miRNAs expression profile associated with the microinflammatory state. Furthermore, microvesicles generated by monocytes treated with uremic toxins induce early senescence and osteogenic markers (BMP2 and miRNA-223-3p) in VSMC.
SN 2296-634X
YR 2020
FD 2020-08-06
LK https://hdl.handle.net/10668/28282
UL https://hdl.handle.net/10668/28282
LA en
DS RISalud
RD Apr 18, 2025