To achieve the goals set out at the beginning of the project, high-content microscopy screenings were performed using a library of microRNA mimics corresponding to all the annotated microRNAs (2,588 mature microRNAs) to analyse fibroblast proliferation and differentiation, and collagen I deposition, as models of the fibroblast activation and extracellular matrix deposition that is seen in vivo. Using this approach, 145 microRNAs that increase and 45 microRNAs that decrease fibroblast differentiation by more than 4-fold relative to control were identified, as well as a number of microRNAs that strongly impact fibroblast proliferation. Furthermore, several miRNAs that decrease collagen I deposition by cardiac fibroblasts were found. Demonstrating the relevance and success of this experimental approach is the identification of master regulators of fibrosis, such as the miR-29 family. Interestingly, close to 200 microRNAs that promote cardiac fibroblast differentiation, but decrease collagen I deposition could be selected. By facilitating the differentiation of fibroblasts into contractile cells, but inhibiting the deposition of extracellular matrix in excess, these microRNAs could promote the regenerative process after a myocardial infarction, yet maintaining the necessary contractile function of the heart, thereby preventing heart failure to ensue.
These results were presented by the fellow at the Keystone’s symposium on RNA-Based Approaches in Cardiovascular Disease held in March 2017 at Keystone Resort, Colorado, USA. A manuscript is being prepared for publication. Furthermore, throughout the duration of the project, the fellow participated in several outreach activities, namely in the European Researcher’s Night and in the Science and Technology week where she visited secondary schools to present her work.
