Unknown

Dataset Information

0

Targeting QKI-7 in vivo restores endothelial cell function in diabetes.


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-?-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.

SUBMITTER: Yang C 

PROVIDER: S-EPMC7393072 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 fact  ...[more]

Similar Datasets

| S-EPMC8034466 | biostudies-literature
2020-02-20 | GSE128565 | GEO
| S-EPMC3087142 | biostudies-literature
| S-EPMC3627729 | biostudies-literature
| S-EPMC7383822 | biostudies-literature
| S-EPMC2365940 | biostudies-literature
| PRJNA528110 | ENA
| S-EPMC5614594 | biostudies-literature
| S-EPMC4021293 | biostudies-literature
| S-EPMC5381285 | biostudies-literature