Long non-coding RNA TUG1 regulates smooth muscle cell differentiation via KLF4-Myocardin axis

Am J Physiol Cell Physiol. 2023 Aug 29. doi: 10.1152/ajpcell.00275.2023. Online ahead of print.ABSTRACTAbdominal Aortic Aneurysms (AAAs) are asymptomatic vascular diseases that have life-threatening outcomes. Smooth-muscle cell (SMC) dysfunction plays an important role in AAA development. The contribution of non-coding genome, specifically the role of long non-coding RNAs (lncRNAs) in SMC dysfunction is relatively unexplored. we investigated the role of lncRNA TUG1 in SMC dysfunction. To identify potential lncRNAs relevant to SMC functionality, lncRNA profiling was performed in angiotensin-II treated SMCs. AAA was induced by angiotensin-II treatment in mice. Transcriptional regulation of TUG1 was studied using promoter luciferase and chromatin-immuno-precipitation experiments. Gain- or loss- of function experiments were performed in-vitro to investigate TUG1-mediated regulation of SMC function. Immunoprecipitation experiments were conducted to elucidate the mechanism underlying TUG1-mediated SMC dysfunction. TUG1 was upregulated in SMCs following angiotensin-II treatment. Similarly, TUG1 levels were elevated in abdominal aorta in a mouse model of angiotensin-II-induced AAA. Further investigations showed that angiotensin-II-induced TUG1 expression could be suppressed by inhibiting Notch-signaling pathway, both in-vitro and in mouse AAA model and that TUG1 is a direct transcriptional target of the Notch-pathway. In aneurysmal tissues, TUG1 expression was inversely correlated wi...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Source Type: research