Journal
MOLECULAR THERAPY
Volume 26, Issue 8, Pages 1996-2007Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2018.05.002
Keywords
-
Categories
Funding
- University of Edinburgh Chancellor's Fellow studentship
- British Heart Foundation (BHF) [FS/11/52/29018, PG/16/58/32275, FS/14/7/30574]
- Edinburgh BHF PhD Program
- Intermediate Fellowship - Oxford British Heart Foundation (BHF) Centre of Research Excellence [RE/08/004/23915]
- BHF Career Re-entry Fellow [FS/16/38/32351]
- Edinburgh BHF Research Excellence Award
Ask authors/readers for more resources
Transforming growth factor beta (TGF-beta) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation of TGF-beta signaling leads to pathological conditions in the vasculature, causing cardiovascular disease and fibrotic disorders. The TGF-beta pathway is critical in endothelial-to-mesenchymal transition (EndMT), but a gap remains in our understanding of the regulation of TGF-beta and related signaling in the endothelium. This study applied a gain- and loss-of function approach and an in vivo model of skin wound healing to demonstrate that miR-148b regulates TGF-beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available