SLUG REGULATES MICRORNAS EXPRESSION IN SMOOTH MUSCLE CELLS

NATALI, LAUTARO; DE LA CRUZ-THEA, BENJAMÍN; RUIZ PAEZ, MICOL; VOLPINI, XIMENA; MEISTER, GUNTER; MUSRI, MELINA M.

Workshop; The neurohumoral control of body fluis and cardiovascular homeostasis in males and females; 2019

Inst. Ferreyra

Vascular Remodeling (VR) is an active process which contributes to the physiopathology of cardiovascular diseases. Smooth muscle cell (SMC) phenotypic alteration play a central role in the development of VR. We previously reported an upregulation of the transcription factor Slug in pulmonary arteries with high VR degree. We found that Slug promotes dedifferentiation and proliferation of SMC, but the underlying mechanisms are still unknown. MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate mRNAs expression. MiRNAs are implicated in the regulation of physiological and pathological states and their expression have been found altered in arteries with VR. In this work we aimed to evaluate if Slug regulates the expression of miRNAs in SMC. To this end, we used an in vitro model of human pulmonary arteries SMC (Lonza) and analyzed miRNAs expression by deep sequencing of small RNAs (Illumina Seq) after knockdown of Slug using a specific siPool against Slug or a control siPool. Candidate miRNAs expression was validated using Northern Blot and mRNA expression by real time PCR. Our results showed a significant change in the expression of a number of miRNAs in Slug knocked down SMC vs the control cells. We validated the increase of miR-let7a, miR-23a and miR-10a, which have been previously implicated in the regulation of proliferation. In conclusion, in SMC, Slug knockdown allows the expression of miR-let7a, miR-23 and miR-10a which in turn might block SMC proliferation. These findings contribute with new knowledge to the biology of SMC.