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.
PB Frontiers Research Foundation
SN 2296-634X
YR 2020
FD 2020-07-16
LK http://hdl.handle.net/10668/16160
UL http://hdl.handle.net/10668/16160
LA en
NO Carmona A, Guerrero F, Jimenez MJ, Ariza F, Agüera ML, Obrero T, et al. Inflammation, Senescence and MicroRNAs in Chronic Kidney Disease. Front Cell Dev Biol. 2020 Aug 6;8:739
DS RISalud
RD Apr 6, 2025