miR-142 Targets TIM-1 in Human Endothelial Cells: Potential Implications for Stroke, COVID-19, Zika, Ebola, Dengue, and Other Viral Infections.
Urna KansakarJessica GambardellaFahimeh VarzidehRoberta AvvisatoStanislovas S JankauskasPasquale MoneAlessandro MatareseJoseph H TaubePublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- endothelial cells
- coronavirus disease
- cell proliferation
- long non coding rna
- angiotensin converting enzyme
- long noncoding rna
- ischemia reperfusion injury
- angiotensin ii
- atrial fibrillation
- zika virus
- transcription factor
- high glucose
- dengue virus
- oxidative stress
- blood brain barrier
- vascular endothelial growth factor
- risk assessment
- high throughput
- risk factors
- human health
- aedes aegypti
- protein kinase