Projects per year
Abstract / Description of output
Transforming growth factor beta (TGF-b) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation of TGF-b signaling leads to pathological conditions in the vasculature, causing cardiovascular disease and fibrotic disorders. The TGF-b pathway is critical in endothelial-tomesenchymal transition (EndMT), but a gap remains in our understanding of the regulation of TGF-b and related signaling in the endothelium. This study applied a gainand loss-of function approach and an in vivo model of skin wound healing to demonstrate that miR-148b regulates TGF-b signaling and has a key role in EndMT, targeting TGFB2 and SMAD2. Overexpression of miR-148b increased EC migration, proliferation, and angiogenesis, whereas its inhibition promoted EndMT. Cytokine challenge decreased miR-148b levels in ECs while promoting EndMT through the regulation of SMAD2. Finally, in a mouse model of skin wound healing, delivery of miR-148b mimics promoted wound vascularization and accelerated closure. In contrast, inhibition of miR-148b enhanced EndMT in wounds, resulting in impaired wound closure that was reversed by SMAD2 silencing. Together, these results demonstrate for the first time that miR-148b is a key factor controlling EndMT and vascularization. This opens new avenues for therapeutic application of miR-148b in vascular and tissue repair.
Original language | English |
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Pages (from-to) | 1996-2007 |
Journal | Molecular Therapy |
Volume | 26 |
Issue number | 8 |
Early online date | 8 May 2018 |
DOIs | |
Publication status | Published - 1 Aug 2018 |
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Dive into the research topics of 'MicroRNA-148b Targets the TGF-β Pathway to Regulate Angiogenesis and Endothelial-to-Mesenchymal Transition during Skin Wound Healing'. Together they form a unique fingerprint.Projects
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Trichoplein: Role for a novel regulator in the endothelial cell function in diabetes
1/09/14 → 31/08/17
Project: Research