Revisiting the cDNA library from Lonomia obliqua caterpillar to identify new molecular targets in inflammatory processes: bioinformatics, in vitro assays and transcriptomics

Abstract

The contact of the skin with the Lonomia obliqua caterpillar bristles leads to poisoning, which is characterized by consumption coagulopathy and secondary fibrinolysis that can lead to hemorrhagic syndrome and, consequently, death. In vivo studies in mice have showed that the raw extract of the caterpillar bristles is capable of inducing the formation of clots by triggering the activation of both prothrombin and factor X, as well as the inflammatory response, with increases leukocyte influx. It is known that the signaling pathways related to inflammation and the coagulation cascade are interrelated. In this regard, the signaling mechanisms involved in diseases related to inflammatory processes such as osteoarthritis (OA) can be investigated. OA is a chronic disease that progresses slowly and is a major cause of disability in the adult population. Through the phenotypic analysis of the L. obliqua cDNA library, using bioinformatics tools, the present project aims the (I) identification of new molecular tools, (II) selection of the structural motifs related to the functions of interest, (III) designing new chemical entities to be synthesized in order to assist the identification and validation of new molecular targets related to inflammatory processes, using chondrocyte models from patients with knee OA. The identification of important new targets in the signaling pathways involved in the inflammatory process is crucial for the development of new and more effective drug candidates to treat OA. (AU)