Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 18, Pages -Publisher
MDPI
DOI: 10.3390/ijms231810242
Keywords
blood-brain barrier; cerebrovascular disease; Chikungunya virus; COVID-19; endothelial cells; HAVCR-1; hBMECs; Japanese encephalitis virus; KIM-1; Lassa virus; Marburg virus; microRNA; miR-142-3p; SARS-CoV-2; stroke; West Nile virus
Funding
- National Institutes of Health (NIH), i.e., National Heart, Lung, and Blood Institute (NHLBI) [R01-HL159062, R01HL164772, R01-HL146691, T32HL144456]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK123259, R01-DK033823]
- National Center for Advancing Translational Sciences (NCATS) [UL1TR002556-06]
- Diabetes Action Research and Education Foundation
- Monique Weill-Caulier Trust
- Irma T. Hirschl Trust
- American Heart Association [AHA20POST35211151, AHA-22POST995561, AHA-21POST836407]
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The study identifies miR-142 as a regulator of TIM-1 and suggests its therapeutic potential in targeting cerebrovascular disorders and systemic complications of coronavirus and other viral infections.
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.
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