microRNAs in the pathophysiology of CKD-MBD: Biomarkers and innovative drugs.
microRNAs comprise a novel class of endogenous small non-coding RNAs that have been shown to be implicated in both vascular damage and bone pathophysiology. Chronic kidney disease-mineral bone disorder (CKD-MBD) is characterized by vessel and bone damage secondary to progressive loss of kidney function. In this review, we will describe how several microRNAs have been implicated, in recent years, in cellular and animal models of CKD-MBD, and have been very recently shown to be deregulated in patients with CKD. Particular emphasis has been placed on the endothelial-specific miR-126, a potential biomarker of endothelial dysfunction, and miR-155 and miR-223, which play a role in both vascular smooth muscle cells and osteoclasts, with an impact on the vascular calcification and osteoporosis process. Finally, as these microRNAs may constitute useful targets to prevent or treat complications of CKD-MBD, we will discuss their potential as innovative drugs, describe how they could be delivered in a timely and specific way to vessels and bone by using the most recent techniques such as nanotechnology, viral vectors or CRISPR gene targeting.
C.U.R.S, Laboratoire INSERM U1088, Chemin du Thil, Université de Picardie Jules Verne, 80025 Amiens Cedex 1, France; Université Paris 13, Sorbonne Paris Cité, UFR SMBH, 74 rue Marcel Cachin, 93017, Bobigny cedex, France.
Valérie
V
Metzinger-Le Meuth
Aix Marseille Univ, INSERM, VRCM, Marseille, France.
Stéphane
S
Burtey
C.U.R.S, Laboratoire INSERM U1088, Chemin du Thil, Université de Picardie Jules Verne, 80025 Amiens Cedex 1, France; Department of Cardiovascular Surgery, Amiens University Hospital, France.
Pierre
P
Maitrias
Division of Nephrology, Ambroise Paré Hospital, APHP, UVSQ University, INSERM U1018 team5, Paris, France.
Ziad A
ZA
Massy
C.U.R.S, Laboratoire INSERM U1088, Chemin du Thil, Université de Picardie Jules Verne, 80025 Amiens Cedex 1, France. Electronic address: laurent.metzinger@u-picardie.fr.
Laurent
L
Metzinger
D000818:Animals; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D055808:Drug Discovery / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*
D005819:Genetic Markers; D035683:MicroRNAs; C524942:MIRN155 microRNA, human; C525067:MIR223, human
Biomarker; Bone; CKD; Gene therapy; Vascular disease; microRNA