MiR-126-3p Is Dynamically Regulated in Endothelial-to-Mesenchymal Transition during Fibrosis

In fibrotic diseases, myofibroblasts derive from a range of cell types including endothelial-to-mesenchymal transition (EndMT). Increasing evidence suggests that miRNAs are key regulators in biological processes but their profile is relatively understudied in EndMT. In human umbilical vein endotheli...

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Vydáno v:International journal of molecular sciences Ročník 22; číslo 16; s. 8629
Hlavní autoři: Jordan, Nina P., Tingle, Samuel J., Shuttleworth, Victoria G., Cooke, Katie, Redgrave, Rachael E., Singh, Esha, Glover, Emily K., Ahmad Tajuddin, Hafiza B., Kirby, John A., Arthur, Helen M., Ward, Chris, Sheerin, Neil S., Ali, Simi
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland MDPI AG 11.08.2021
MDPI
Témata:
Animals
Cell Transdifferentiation - genetics
Cells, Cultured
Endothelial Cells - pathology
Endothelial Cells - physiology
Fibroblasts
Fibrosis - genetics
Gene expression
Heart attacks
Human Umbilical Vein Endothelial Cells - metabolism
Human Umbilical Vein Endothelial Cells - pathology
Human Umbilical Vein Endothelial Cells - physiology
Humans
Kidney - metabolism
Kidney - pathology
Kidneys
Mesenchymal Stem Cells - physiology
Mice
Mice, Inbred C57BL
MicroRNAs
MicroRNAs - physiology
Myocardium - metabolism
Myocardium - pathology
Myofibroblasts - metabolism
Myofibroblasts - pathology
Proteins
Transplants & implants
endothelial-to-mesenchymal transition
microRNA
miR-126
fibrosis
ISSN:1422-0067, 1661-6596, 1422-0067
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Shrnutí:In fibrotic diseases, myofibroblasts derive from a range of cell types including endothelial-to-mesenchymal transition (EndMT). Increasing evidence suggests that miRNAs are key regulators in biological processes but their profile is relatively understudied in EndMT. In human umbilical vein endothelial cells (HUVEC), EndMT was induced by treatment with TGFβ2 and IL1β. A significant decrease in endothelial markers such as VE-cadherin, CD31 and an increase in mesenchymal markers such as fibronectin were observed. In parallel, miRNA profiling showed that miR-126-3p was down-regulated in HUVECs undergoing EndMT and over-expression of miR-126-3p prevented EndMT, maintaining CD31 and repressing fibronectin expression. EndMT was investigated using lineage tracing with transgenic Cdh5-Cre-ERT2; Rosa26R-stop-YFP mice in two established models of fibrosis: cardiac ischaemic injury and kidney ureteric occlusion. In both cardiac and kidney fibrosis, lineage tracing showed a significant subpopulation of endothelial-derived cells expressed mesenchymal markers, indicating they had undergone EndMT. In addition, miR-126-3p was restricted to endothelial cells and down-regulated in murine fibrotic kidney and heart tissue. These findings were confirmed in patient kidney biopsies. MiR-126-3p expression is restricted to endothelial cells and is down-regulated during EndMT. Over-expression of miR-126-3p reduces EndMT, therefore, it could be considered for miRNA-based therapeutics in fibrotic organs.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22168629