Fibrosis is a universal finding in chronic allograft dysfunction, and it is characterized by an accumulation of extracellular matrix. The precise source of the myofibroblasts responsible for matrix deposition is not understood, and pharmacological strategies for prevention or treatment of fibrosis remain limited. One source of myofibroblasts in fibrosis is an endothelial-to-mesenchymal transition (EndMT), a process first described in heart development and involving endothelial cells undergoing a phenotypic change to become more like mesenchymal cells. Recently, lineage tracing of endothelial cells in mouse models allowed studies of EndMT in vivo and reported 27% to 35% of myofibroblasts involved in cardiac fibrosis and 16% of isolated fibroblasts in bleomycin-induced pulmonary fibrosis to be of endothelial origin. Over the past decade, mature microRNAs (miRNAs) have increasingly been described as key regulators of biological processes through repression or degradation of targeted mRNA. The stability and abundance of miRNAs in body fluids make them attractive as potential biomarkers, and progress is being made in developing miRNA targeted therapeutics. In this review, we will discuss the evidence of miRNA regulation of EndMT from in vitro and in vivo studies and the potential relevance of this to heart, lung, and kidney allograft dysfunction.
1 Institute of Cellular Medicine, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
2 Institute of Cellular Medicine, Newcastle University, United Kingdom.
Received 16 June 2018. Revision received 14 November 2018.
Accepted 15 December 2018.
This work was supported by The British Heart Foundation (grant FS/15/19/31327) and a Marie Curie Grant from the European Commission (POSAT 606979 and garnt FP7-PEOPLE-2013-ITN). The research group is supported by the NIHR Newcastle Biomedical Research Centre.
The authors declare no conflicts of interest.
E.K.G. contributed to the data collection, analysis, and interpretation and drafted the article. N.J. and S.A. contributed to the conception of the work and critically revised the article. N.S.S. critically revised the article. All authors approved the final version for submission.
Correspondence: Emily K. Glover, MBBS, BA, Institute of Cellular Medicine, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, United Kingdom. (email@example.com).