Small-noncoding YRNA3 regulates smooth muscle cells plasticity

PISANO V; MEISTER G; DE LA CRUZ THEA B; BARBERÀ JA; PEINADO V ; MUSRI M

Jornada; I Jornadas de RNA no codificantes; 2017

Pathological vascular remodeling consists in structural changes of the arterial wall related with excessive proliferation and migration of smooth muscle cells (SMC). This highly specialized cell type is able to change from a contractile-differentiated phenotype to a proliferative-dedifferentiated state. This intrinsic plasticity allows SMC to respond to environmental cues and adapt the vasculature to the organism requirements. However, during the development of vascular disease, the cells lost this function and stays in a dedifferentiated phenotype, which is characterized by decreased expression of specific markers as well as increased rates of proliferation and migration. YRNAs are a class of small-noncoding RNAs that are highly conserved in mammals. These molecules were first described for they association with the Ro60 and La Ribonucleoproteins (RNP), best known for their involvement in connective tissue diseases. There are 4 different YRNAs in human (hY1, hY3, hY4 and hY5). Overexpression of YRNAs was documented in different tumors and in the last years, high levels of YRNAs were reported in a number of microvesicles. YRNAs are important for chromosomal DNA replication as well as cell proliferation. However, the function of YRNAs in cell differentiation has never been studied. Our objective was to investigate the role of YRNAs in SMCs phenotypic change. Primary human pulmonary artery SMC were used in this study. In order to knockdown the expression of YRNAs, we transfected small interfering RNAs (siRNA) targeting their central loop. Expression of YRNAs was measured by northern blot while expression of SMC specific markers was evaluated by real time PCR, immunofluorescence and northern blot. We successfully blocked the expression of hY1, hY3 and hY4 in proliferative SMC. Results showed a significant induction of SMC markers in hY3-depleted cells after 24 and 48 hour of sihY3 transfection. We conclude that hY3 have a key role in the regulation of SMC phenotype.