Non-coding RNAs in the pathogenesis of SSc
Advancements in deep sequencing and microarray technologies have pointed out the fact that the majority of the genome is transcribed and that a large amount of transcribed RNA does not encode for proteins. Long noncoding RNAs (LncRNAs) are a novel class of non-protein coding transcripts arbitrary defined as RNA fragments longer than 200 bp, despite a broad spectrum of diverse biological roles, a common theme is emerging: lncRNAs drive the formation of ribonucleoprotein complexes which in turn regulate gene expression at several level. MicroRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs.
Quelle: Wahlestedt C. Nature Reviews Drug Discovery 12, 433-446 (2013)
Given the complexity and the multilayered structure of the SSc pathogenesis, we hypothesized that lncRNAs and microRNAs could play a significant role in this disease development. In order to have a better insight at the molecular mechanism underlying this pathology, we aim to identify and characterize the function of ncRNAs involved in SSc. We use primary cells culture of dermal fibroblasts from biopsies of SSc patients, in vitro cell stimulation with cytokines, knockdown of gene expression using siRNA or LNA GapmeRs and classical molecular biology techniques to analyze RNA and protein level. In the future we would like to confirm our in vitro findings in animal models representative for SSc like Fra-2 transgenic mouse, bleomycin mouse model or TSK-1 mouse.