miR-142 Targets TIM-1 in Human Endothelial Cells: Potential Implications for Stroke, COVID-19, Zika, Ebola, Dengue, and Other Viral Infections

Urna Kansakar, Jessica Gambardella, Fahimeh Varzideh, Roberta Avvisato, Stanislovas S. Jankauskas, Pasquale Mone, Alessandro Matarese, Gaetano Santulli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number10242
JournalInternational Journal of Molecular Sciences
Volume23
Issue number18
DOIs
StatePublished - Sep 2022

Keywords

  • COVID-19
  • Chikungunya virus
  • HAVCR-1
  • Japanese encephalitis virus
  • KIM-1
  • Lassa virus
  • Marburg virus
  • SARS-CoV-2
  • West Nile virus
  • blood–brain barrier
  • cerebrovascular disease
  • endothelial cells
  • hBMECs
  • miR-142-3p
  • microRNA
  • stroke

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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