ECE2022 Eposter Presentations Diabetes, Obesity, Metabolism and Nutrition (318 abstracts)
Regulation of glycemic variability in endothelial model: cross-talk between miRNAs and microfilaments in the activation of early fibrotic pathways
Lucia La Sala 1 , Pamela Senesi 2 , Daniele Capoitanio 2 , Elena Tagliabue 1 , Anna Ferrulli 2 , Ileana Terruzzi 2 & Livio Luzi 1,2
1Multimedica, Lab of Cardiovascular and Dysmetabolic Diseases, Milano, Italy; 2University of Milan, Milano, Italy
Glycemic variability (GV), a complex phenomenon affecting subjects with diabetes, is one of the main contributors to the risk to develop both acute and long-term complications in type 1 (T1D) and type 2 (T2D) subjects. DNA double-strand breaks, apoptosis, overgeneration of reactive oxygen species (ROS) and the induction of some regulatory micro-RNAs, sustain the ominous mechanisms mainly attributable to GV. The characteristic cellular phenotype induced by GV is scarcely defined. Aims of this study are: 1) to describe a global pattern about the regulation of the major proteins differentially expressed in a cellular (human endothelial cells) model of GV and 2) the role of microRNAs on the pathways activated during the in-vitro long-term exposures to GV. We utilized human endothelial cells exposed for 21 days to high and oscillating glucose concentration (25 mM and 5-25 mM, respectively). The omic-based analysis integrating proteomic (2D-DIGE and MALDI/TOF) and miRNA discovery, identified a dataset of proteins and micro-RNAs differentially regulated by the oscillating and high glucose conditions. In particular, microarray of immunoprecipitated target bound to miR-146a-5p identified the main mRNA transcripts in this model. We found a protein identified both in proteomic and microarray experiments, vimentin, which is the principal protein involved in the activation of fibrotic pathways. Immunofluorescence analysis showed that the increased expression of vimentin is due to silencing of miR-146a-5p. Our set of data constitutes the “Proof of Principle” about the ability of the omic-approaches (proteomic analyses coupled with miRNome) to reveal potential biomarkers for the GV model. Future perspective is to draw the GV cellular signature along with associated functions and mechanisms.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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