Notch regulated long non-coding RNA TUG1 regulates smooth muscle cell differentiation in aortic aneurysm
Kumarswamy, R.; Ravi, A. B.
Show abstract
Abdominal Aortic Aneurysms (AAAs) are asymptomatic vascular diseases with life threatening outcomes. Smooth-muscle cell (SMC) dysfunction plays an important role in AAA development. The contributions of non-coding genome, specifically the role of long non-coding RNAs (lncRNAs) in SMC dysfunction are relatively unexplored. We investigated the role of lncRNA TUG1 in the pathology of AAA. TUG1 was identified through lncRNA profiling in Angiotensin-II (Ang-II) treated SMCs. TUG1 was upregulated in Ang-II treated SMCs in vitro and its expression increased with progression of aneurysm in mouse model of Ang-II induced AAA. Ang-II induced TUG1 was blunted by inhibition of Notch signaling and TUG1 is demonstrated to be a transcriptional target of Notch. AAA tissues exhibited inversely correlated expression of TUG1 and SMC contractile markers. TUG1 knock-down via siRNA/shRNA increased SMC differentiation. ChIP, DNA-RNA IP, and RNA-IP experiments demonstrated that TUG1 interacts with transcriptional repressor KLF4 and aides in its recruitment to Myocardin promoter, thereby repressing SMC differentiation. In summary, we show a novel role for lncRNA TUG1 in Ang-II induced AAA wherein it modulates SMC differentiation via KLF4-Myocardin axis.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Disruption of the Novel Nested Gene Aff3ir Mediates Disturbed Flow-Induced Atherosclerosis in Mice 95%
- Rudhira-mediated microtubule stability controls TGFβ signaling during mouse vascular development 93%
- Oxidized low-density lipoprotein potentiates angiotensin II-induced Gq activation through the AT1-LOX1 receptor complex: Implications for renal dysfunction 93%
Similar papers in this journal
- Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice 95%
- Aberrant mechanosensitive signaling underlies activation of vascular endothelial xanthine oxidoreductase that promotes aortic aneurysm formation in Marfan syndrome 94%
- Gut microbial metabolite imidazole propionate impairs endothelial cell function and promotes the development of atherosclerosis 94%
Similar papers in this journal
- Crosstalk of platelets with macrophages and fibroblasts aggravates inflammation, aortic wall stiffening, and osteopontin release in abdominal aortic aneurysm 93%
- Endothelial Rho kinase controls blood vessel integrity and angiogenesis 92%
- Enhanced intracranial aneurysm development in a rat model of polycystic kidney disease. 92%
Similar papers in this journal
- Using TCR and BCR sequencing to unravel the role of T and B cells in abdominal aortic aneurysm 93%
- Endothelial Nitric Oxide Synthase (eNOS) S1176 phosphorylation status governs atherosclerotic lesion formation 92%
- Common variation in EDN1 regulatory regions highlights the role of PPARγ as a key regulator of Endothelin in vitro 91%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.