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MicroRNAs in kidney physiology and disease

Key Points

  • MicroRNAs (miRNAs) are key players in kidney development and physiology

  • Transforming growth factor β1 is a major regulator of kidney fibrosis; its signalling is finely regulated by miRNAs

  • miRNAs contribute to both the induction and progression of chronic kidney disease (CKD)

  • Current translational research on miRNAs in kidney disease is mainly focused on developing reliable biomarkers for diagnosis and prognosis of CKD and renal transplantation

  • miRNAs represent novel therapeutic targets for CKD, but delivery and safety issues must be taken into account before translation into clinical practice

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. They have important roles during kidney development, homeostasis and disease. In particular, miRNAs participate in the onset and progression of tubulointerstitial sclerosis and end-stage glomerular lesions that occur in various forms of chronic kidney disease (CKD). Therefore, miRNAs represent potential new therapeutic targets for a debilitating disease that continues to increase in prevalence worldwide and for which fully effective therapies are lacking. Several lines of research aimed at improving common CKD diagnostic tools and avoiding invasive kidney biopsies have also identified circulating miRNAs as possible diagnostic and even prognostic biomarkers of kidney disease. This Review discusses current understanding of the function of miRNAs in CKD, focusing on functions specifically involved in the transforming growth factor β1 pathway, which is activated in CKD. miRNAs that, according to available evidence, seem to be involved in diabetic nephropathy, IgA nephropathy, lupus nephritis, polycystic kidney disease and graft rejection, are also discussed.

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Figure 1: Interplay between TGF-β1/Smad signalling and the miRNA machinery.
Figure 2: miRNA-regulatory networks in proximal tubular epithelial cells and mesangial cells in response to TGF-β1, and in podocytes in response to TGF-β1 and high glucose.

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Acknowledgements

We would like to thank S. Tomasoni and D. Macconi for helpful discussions regarding the manuscript.

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P.T. researched data for the article. P.T. and A.B. contributed substantially to discussion of the article's content and wrote the article. A.B. and G.R. reviewed and edited the manuscript before submission.

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Correspondence to Ariela Benigni.

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Trionfini, P., Benigni, A. & Remuzzi, G. MicroRNAs in kidney physiology and disease. Nat Rev Nephrol 11, 23–33 (2015). https://doi.org/10.1038/nrneph.2014.202

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