miR-142 Targets TIM-1 in Human Endothelial Cells: Potential Implications for Stroke, COVID-19, Zika, Ebola, Dengue, and Other Viral Infections.
miR-142 Targets TIM-1 in Human Endothelial Cells: Potential Implications for Stroke, COVID-19, Zika, Ebola, Dengue, and Other Viral Infections.
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DOI：
10.3390/ijms231810242
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发表时间：
2022-09-06
影响因子：
5.6
通讯作者：
Santulli, Gaetano
中科院分区：
文献类型：
--
作者：
Kansakar, Urna;Gambardella, Jessica;Varzideh, Fahimeh;Avvisato, Roberta;Jankauskas, Stanislovas S.;Mone, Pasquale;Matarese, Alessandro;Santulli, Gaetano
关键词：
T细胞免疫球蛋白和粘蛋白结构域1（TIM-1）最近被鉴定为除血管紧张素转换酶2（ACE 2）、跨膜丝氨酸蛋白酶2（TMPRSS 2）、神经纤毛蛋白1等之外的参与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在人类细胞中内化的因子之一。我们假设特定的microRNA可以靶向TIM-1，对2019冠状病毒病（COVID-19）患者的管理具有潜在意义。通过结合生物信息学分析和功能测定，我们鉴定出miR-142是TIM-1转录的特异性调节因子。由于TIM-1在血脑屏障（BBB）水平参与内皮功能的调节，并且其水平已被证明与中风和脑缺血再灌注损伤相关，我们验证了miR-142作为人脑微血管内皮细胞（hBMEC）中TIM-1的功能调节剂。综上所述，我们的研究结果表明，miR-142靶向TIM-1，代表了一种新的策略，针对脑血管疾病，以及全身并发症的SARS-CoV-2和其他病毒感染。
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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DOI：
10.1186/s13054-021-03731-1
发表时间：
2021-08-25
期刊：
Critical care (London, England)
影响因子：
--
作者：
Gambardella J;Coppola A;Izzo R;Fiorentino G;Trimarco B;Santulli G
通讯作者：
Santulli G
影响因子：
6
作者：
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通讯作者：
Achim, CL
影响因子：
8.8
作者：
Dejarnac, Ophelie;Hafirassou, Mohamed Lamine;Amara, Ali
通讯作者：
Amara, Ali
影响因子：
4.3
作者：
Dama E;Melocchi V;Mazzarelli F;Colangelo T;Cuttano R;Di Candia L;Ferretti GM;Taurchini M;Graziano P;Bianchi F
通讯作者：
Bianchi F
DOI：
10.1073/pnas.2113874119
发表时间：
2022-02-08
影响因子：
11.1
作者：
Amraei R;Xia C;Olejnik J;White MR;Napoleon MA;Lotfollahzadeh S;Hauser BM;Schmidt AG;Chitalia V;Mühlberger E;Costello CE;Rahimi N
通讯作者：
Rahimi N