Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 27, Issue 3, Pages 824-834Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2014050520
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Funding
- Plan Nacional de Investigacion, Desarrollo e Innovacion (I+D+i)
- Plan Estatal de I+D+i
- Instituto de Salud Carlos III (ISCIII)-Fondo Europeo de Desarrollo Regional Grants [PI07/0893, PI10/0896, PI13/00497]
- Plan de Ciencia, Tecnologia e Innovacion del Principado de Asturias [GRUPIN14-028]
- Fundacion para el Fomento en Asturias de la Investigacion Cientifica Aplicada y la Tecnologia (FICYT)
- Instituto Reina Sofia de Investigacion Nefrologica
- Fundacion Renal Inigo Alvarez de Toledo
- Red de Investigacion Renal (REDinREN) from ISCIII [RD06/0016, RD12/0021]
- ISCIII [PI09/0415]
- Sara Borrell-FICYT [CD11/00258]
- ISCIII-RedInRen Grant [RD06/0016]
- ISCIII FICYT Grant [CA10/01327]
- FICYT
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Vascular calcification is a frequent cause of morbidity and mortality in patients with CKD, and the general population: The common association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. Because microRNAs (miRs) are involved in the transdifferentiation of vascular smooth muscle cells into osteoblast-like cells, we investigated whether miRs implicated in osteoblast differentiation and bone formation are involved in vascular calcification. Different levels of uremia, hyper-phosphatemia, and aortic calcification were induced by feeding nephrectomized rats a normal or, high phosphorus diet for 12 or 20 weeks, at which times the levels of eight miRs (miR-29b, miR-125, miR-133b, miR-135, miR-141, miR-200a, miR-204, and miR-211) in the aorta were analyzed. Compared with controls and uremic rats fed a normal diet, uremic rats fed a high-phosphorous diet had lower levels of miR-133b and miR-211 and higher levels of miR-29b that correlated respectively with greater expression of osteogenic RUNX2 and with lower expression of several inhibitors of osteoblastic differentiation. Uremia per se mildly reduced miR-133b levels only. Similar results were obtained in two in vitro models of vascular calcification (uremic serum and high-calcium and phosphorus medium), and experiments using antagomirs and mimics to modify miR-29b, nniR-133b, and miR-211 expression levels in these models confirmed that these miRs regulate the calcification process. We conclude that miR-29b, miR-133b, and miR-211 have direct roles in the vascular smooth muscle calcification induced by high phosphorus and may be new therapeutic targets in the management of vascular calcification.
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