miR‐145‐5p profibrotic activity in RDEB

Abstract

Summary Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and highly disabling genetic disease. RDEB hallmarks are skin fragility, constant blistering, and defective wound healing leading to inflammation and fibrosis, which means tissue hardening. Fibrosis underlies major RDEB complications, including limb deformities and cancer, and preventing it is a strategy to improve the disease course. Despite the identification of several molecules that are deregulated in RDEB fibrosis, the disease mechanisms are not fully known. Our genetic code contains the information to produce RNA molecules, called messenger RNAs, which serve to build the proteins forming our body. However, a large family of RNA molecules, called microRNAs, are not transformed into proteins, but regulate the amount of proteins produced. The altered function of microRNAs contributes to the development of many diseases. This study, performed at Bambino Gesù Children's Hospital in Italy, aimed to identify and characterize the role of microRNAs that are altered in RDEB patients and contribute to their skin fibrosis. This laboratory study used a cell type, the fibroblast, which populates the skin and is a major player in fibrosis. The authors observed that some microRNAs are more abundant in fibroblasts obtained from RDEB patients as compared to cells from healthy individuals, and demonstrated that one of them, the miR‐145‐5p, fuels fibrosis. The researchers switched off the miR‐145‐5p in RDEB fibroblasts and then studied fibroblast ability to contract, proliferate, and move, all activities that are increased in fibrosis. Blocking miR‐145‐5p reduced the contractility, proliferation and migration of RDEB fibroblasts, and determined the reduction of various contractile and pro‐fibrotic (fibrosis causing) molecules. In conclusion, the authors have discovered a novel microRNA that contributes to the development of fibrosis in RDEB, and described its mode of action. These findings help us to understand more about the disease and possible targets for future treatment.