Department of Medicine, Division of Cardiology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, NY 10461, USA.
AORN "Antonio Cardarelli", 80131 Naples, Italy.
Int J Mol Sci. 2022 Sep 6;23(18):10242. doi: 10.3390/ijms231810242.
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.
T 细胞免疫球蛋白和粘蛋白结构域 1（TIM-1）最近被确定为人类细胞中冠状病毒 2（SARS-CoV-2）内化的相关因素之一，除此之外还有血管紧张素转换酶 2（ACE2）、跨膜丝氨酸蛋白酶 2（TMPRSS2）、神经纤毛蛋白 1 等。我们假设特定的 microRNA 可以靶向 TIM-1，这可能对患有 2019 年冠状病毒病（COVID-19）的患者的治疗有影响。通过结合生物信息学分析和功能测定，我们确定了 miR-142 是 TIM-1 转录的特定调节因子。由于 TIM-1 已被牵连到血脑屏障（BBB）内皮功能的调节，并且其水平与中风和脑缺血再灌注损伤有关，因此我们验证了 miR-142 是人类脑微血管内皮细胞（hBMECs）中 TIM-1 的功能调节剂。总之，我们的结果表明，miR-142 靶向 TIM-1，这代表了一种针对脑血管疾病以及 SARS-CoV-2 和其他病毒感染的全身并发症的新策略。
