| Title : Targeting QKI-7 in vivo restores endothelial cell function in diabetes - Yang_2020_Nat.Commun_11_3812 |
| Author(s) : Yang C , Eleftheriadou M , Kelaini S , Morrison T , Gonzalez MV , Caines R , Edwards N , Yacoub A , Edgar K , Moez A , Ivetic A , Zampetaki A , Zeng L , Wilkinson FL , Lois N , Stitt AW , Grieve DJ , Margariti A |
| Ref : Nat Commun , 11 :3812 , 2020 |
|
Abstract :
Vascular endothelial cell (EC) dysfunction plays a key role in diabetic complications. This study discovers significant upregulation of Quaking-7 (QKI-7) in iPS cell-derived ECs when exposed to hyperglycemia, and in human iPS-ECs from diabetic patients. QKI-7 is also highly expressed in human coronary arterial ECs from diabetic donors, and on blood vessels from diabetic critical limb ischemia patients undergoing a lower-limb amputation. QKI-7 expression is tightly controlled by RNA splicing factors CUG-BP and hnRNPM through direct binding. QKI-7 upregulation is correlated with disrupted cell barrier, compromised angiogenesis and enhanced monocyte adhesion. RNA immunoprecipitation (RIP) and mRNA-decay assays reveal that QKI-7 binds and promotes mRNA degradation of downstream targets CD144, Neuroligin 1 (NLGN1), and TNF-alpha-stimulated gene/protein 6 (TSG-6). When hindlimb ischemia is induced in diabetic mice and QKI-7 is knocked-down in vivo in ECs, reperfusion and blood flow recovery are markedly promoted. Manipulation of QKI-7 represents a promising strategy for the treatment of diabetic vascular complications. |
| PubMedSearch : Yang_2020_Nat.Commun_11_3812 |
| PubMedID: 32732889 |
Yang C, Eleftheriadou M, Kelaini S, Morrison T, Gonzalez MV, Caines R, Edwards N, Yacoub A, Edgar K, Moez A, Ivetic A, Zampetaki A, Zeng L, Wilkinson FL, Lois N, Stitt AW, Grieve DJ, Margariti A (2020)
Targeting QKI-7 in vivo restores endothelial cell function in diabetes
Nat Commun
11 :3812
Yang C, Eleftheriadou M, Kelaini S, Morrison T, Gonzalez MV, Caines R, Edwards N, Yacoub A, Edgar K, Moez A, Ivetic A, Zampetaki A, Zeng L, Wilkinson FL, Lois N, Stitt AW, Grieve DJ, Margariti A (2020)
Nat Commun
11 :3812