miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19

被引:114
作者
Matarese, Alessandro [1 ,2 ]
Gambardella, Jessica [1 ,3 ,4 ,5 ]
Sardu, Celestino [6 ,7 ]
Santulli, Gaetano [1 ,3 ,4 ,5 ]
机构
[1] Albert Einstein Coll Med, Einstein Inst Aging Res, Wilf Family Cardiovasc Res Inst, Dept Med, Bronx, NY 10461 USA
[2] AORN Antonio Cardarelli, I-80100 Naples, Italy
[3] Univ Naples Federico II, Dept Adv Biomed Sci, I-80131 Naples, Italy
[4] Int Translat Res & Med Educ Consortium ITME, I-80131 Naples, Italy
[5] Albert Einstein Coll Med, Dept Mol Pharmacol, Fleischer Inst Diabet & Metab FIDAM, Einstein Mt Sinai Diabet Res Ctr ESDRC, Bronx, NY 10461 USA
[6] Univ Campania Luigi Vanvitelli, Dept Adv Med & Surg Sci, I-80138 Naples, Italy
[7] Int Univ Hlth & Med Sci S Camillo, Dept Med Sci, I-00131 Rome, Italy
关键词
ACE2; coronavirus; COVID-19; endothelium; epigenetics; HMVEC-L; HUVEC; lung; microRNA; miR-98-5p; non-coding RNA; SARS-CoV-2; INDUCED-APOPTOSIS; SMOOTH-MUSCLE; MICRORNAS; ACE2; SARS-COV-2; INJURY; AXIS;
D O I
10.3390/biomedicines8110462
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The two main co-factors needed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Here, we focused on the study of microRNAs that specifically target TMPRSS2. Through a bioinformatic approach, we identified miR-98-5p as a suitable candidate. Since we and others have shown that endothelial cells play a pivotal role in the pathogenesis of the coronavirus disease 2019 (COVID-19), we mechanistically validated miR-98-5p as a regulator of TMPRSS2 transcription in two different human endothelial cell types, derived from the lung and from the umbilical vein. Taken together, our findings indicate that TMPRSS2 represents a valid target in COVID-19 treatment, which may be achieved by specific non-coding-RNA approaches.
引用
收藏
页码:1 / 10
页数:10
相关论文
共 77 条
[1]   Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 [J].
Ackermann, Maximilian ;
Verleden, Stijn E. ;
Kuehnel, Mark ;
Haverich, Axel ;
Welte, Tobias ;
Laenger, Florian ;
Vanstapel, Arno ;
Werlein, Christopher ;
Stark, Helge ;
Tzankov, Alexandar ;
Li, William W. ;
Li, Vincent W. ;
Mentzer, Steven J. ;
Jonigk, Danny .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (02) :120-128
[2]   Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety [J].
Akhtar, Saghir ;
Benter, Ibrahim F. ;
Danjuma, Mohammed, I ;
Doi, Suhail A. R. ;
Hasan, Syed S. ;
Habib, Abdella M. .
JOURNAL OF DRUG TARGETING, 2020, 28 (7-8) :683-699
[3]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[4]   ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy [J].
Asselta, Rosanna ;
Paraboschi, Elvezia Maria ;
Mantovani, Alberto ;
Duga, Stefano .
AGING-US, 2020, 12 (11) :10087-10098
[5]   Non-coding RNAs: update on mechanisms and therapeutic targets from the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart [J].
Bar, Christian ;
Chatterjee, Shambhabi ;
Pires, Ines Falcao ;
Rodrigues, Patricia ;
Sluijter, Joost P. G. ;
Boon, Reinier A. ;
Nevado, Rosa M. ;
Andres, Vicente ;
Sansonetti, Marida ;
de Windt, Leon ;
Ciccarelli, Michele ;
Hamdani, Nazha ;
Heymans, Stephane ;
Videira, Raquel Figuinha ;
Tocchetti, Carlo G. ;
Giacca, Mauro ;
Zacchigna, Serena ;
Engelhardt, Stefan ;
Dimmeler, Stefanie ;
Madonna, Rosalinda ;
Thum, Thomas .
CARDIOVASCULAR RESEARCH, 2020, 116 (11) :1805-1819
[6]   miR-98 reduces endothelial dysfunction by protecting blood-brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model [J].
Bernstein, David L. ;
Zuluaga-Ramirez, Viviana ;
Gajghate, Sachin ;
Reichenbach, Nancy L. ;
Polyak, Boris ;
Persidsky, Yuri ;
Rom, Slava .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2020, 40 (10) :1953-1965
[7]   The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation [J].
Boesmueller, Hans ;
Traxler, Selina ;
Bitzer, Michael ;
Haeberle, Helene ;
Raiser, Wolfgang ;
Nann, Dominik ;
Frauenfeld, Leonie ;
Vogelsberg, Antonio ;
Klingel, Karin ;
Fend, Falko .
VIRCHOWS ARCHIV, 2020, 477 (03) :349-357
[8]   The ACE2/Ang-(1-7)/Mas axis can inhibit hepatic insulin resistance [J].
Cao, Xi ;
Yang, Fang-Yuan ;
Xin, Zhong ;
Xie, Rong-Rong ;
Yang, Jin-Kui .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2014, 393 (1-2) :30-38
[9]   A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema [J].
Chan, Hwei Wuen ;
Yang, Binxia ;
Wong, Wendy ;
Blakeley, Paul ;
Seah, Ivan ;
Tan, Queenie Shu Woon ;
Wang, Haofei ;
Bhargava, Mayuri ;
Lin, Hazel Anne ;
Chai, Charmaine H. C. ;
Mangunkusumo, Erlangga Ariadarma ;
Thet, Naing ;
Yuen, Yew Sen ;
Sethi, Raman ;
Wang, Si ;
Hunziker, Walter ;
Lingam, Gopal ;
Su, Xinyi .
JOURNAL OF CLINICAL MEDICINE, 2020, 9 (09) :1-18
[10]   MicroRNA-98 rescues proliferation and alleviates ox-LDL-induced apoptosis in HUVECs by targeting LOX-1 [J].
Chen, Zhibo ;
Wang, Mian ;
He, Qiong ;
Li, Zilun ;
Zhao, Yang ;
Wang, Wenjian ;
Ma, Jieyi ;
Li, Yongxin ;
Chang, Guangqi .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2017, 13 (05) :1702-1710