Targeting QKI-7 in vivo restores endothelial cell function in diabetes
Chunbo Yang, Magdalini Eleftheriadou, Sophia Kelaini, Thomas Morrison, Marta Vilà González, Rachel Caines, Nicola Edwards, Andrew Yacoub, Kevin Edgar, Arya Moez, Aleksandar Ivetic, Anna Zampetaki, Lingfang Zeng, Fiona L. Wilkinson, Noemi Lois, Alan W. Stitt, David J. Grieve & Andriana Margariti.
Nat Commun. 2020 Jul 30;11(1):3812. doi: 10.1038/s41467-020-17468-y
Key findings
1. QKI-7 is significant upregulated in diabetic human iPS cell-derived ECs, and in blood vessels from diabetic critical limb ischemia patients.
2. The expression of QKI-7 is tightly controlled by RNA splicing factors-CUG-BP and hnRNPM through direct binding in diabetic ECs.
3. QKI-7 upregulation is correlated with disrupted cell barrier, compromised angiogenesis and enhanced monocyte adhesion.
4. When QKI-7 was knocked-down in vivo in ECs in the hindlimb ischemia model in diabetic mice, reperfusion and blood flow recovery were promoted.
5. Manipulation of QKI-7 represents a promising strategy for the treatment of diabetic vascular complications.
