ABSTRACT
T-cell immunoglobulin and mucin domain 1 (TIM-1) has been recently identified as one of the factors involved in the internalization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells, in addition to angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), neuropilin-1, and others. We hypothesized that specific microRNAs could target TIM-1, with potential implications for the management of patients suffering from coronavirus disease 2019 (COVID-19). By combining bioinformatic analyses and functional assays, we identified miR-142 as a specific regulator of TIM-1 transcription. Since TIM-1 has been implicated in the regulation of endothelial function at the level of the blood-brain barrier (BBB) and its levels have been shown to be associated with stroke and cerebral ischemia-reperfusion injury, we validated miR-142 as a functional modulator of TIM-1 in human brain microvascular endothelial cells (hBMECs). Taken together, our results indicate that miR-142 targets TIM-1, representing a novel strategy against cerebrovascular disorders, as well as systemic complications of SARS-CoV-2 and other viral infections.
Subject(s)
Endothelial Cells/pathology , Hepatitis A Virus Cellular Receptor 1/metabolism , MicroRNAs , Angiotensin-Converting Enzyme 2 , COVID-19 , Dengue , Endothelial Cells/metabolism , Hemorrhagic Fever, Ebola , Humans , Immunoglobulins , MicroRNAs/genetics , Mucins , Neuropilin-1/genetics , Peptidyl-Dipeptidase A , SARS-CoV-2 , Stroke , Zika Virus , Zika Virus InfectionABSTRACT
The biological abilities of interleukin6 (IL6) have been under investigation for nearly 40 years. IL6 works through an interaction with the complex peptide IL6 receptor (IL6R). IL6 is built with four αchain nanostructures, while two different chains, IL6Rα (gp80) and gp130/IL6ß (gp130), are included in IL6R. The threedimensional shapes of the six chains composing the IL6/IL6R complex are the basis for the nanomolecular roles of IL6 signalling. Genes, pseudogenes and competitive endogenous RNAs of IL6 have been identified. In the present review, the roles played by miRNA in the posttranscriptional regulation of IL6 expression are evaluated. mRNAs are absorbed via the 'sponge' effect to dynamically balance mRNA levels and this has been assessed with regard to IL6 transcription efficiency. According to current knowledge on molecular and nanomolecular structures involved in active IL6 signalling, two different IL6 models have been proposed. IL6 mainly has functions in inflammatory processes, as well as in cognitive activities. Furthermore, the abnormal production of IL6 has been found in patients with severe acute respiratory syndrome coronavirus 2 (SARSCoV2; also known as COVID19). In the present review, both inflammatory and cognitive IL6 models were analysed by evaluating the cytological and histological locations of IL6 signalling. The goal of this review was to illustrate the roles of the classic and transsignalling IL6 pathways in endocrine glands such as the thyroid and in the central nervous system. Specifically, autoimmune thyroid diseases, disorders of cognitive processes and SARSCoV2 virus infection have been examined to determine the contribution of IL6 to these disease states.