Expression and co-expression analyses of TMPRSS2, a key element in COVID-19
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Expression and co-expression analyses of TMPRSS2, a key element in COVID-19 Francesco Piva 1 & Berina Sabanovic 1 & Monia Cecati 1 & Matteo Giulietti 1 Received: 29 June 2020 / Accepted: 28 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The ACE2 receptor is, so far, the best-known host factor for SARS-CoV-2 entry, but another essential element, the TMPRSS2 protease, has recently been identified. Here, we have analysed TMPRSS2 expression data in the lung correlating them with age, sex, diabetes, smoking habits, exposure to pollutant and other stimuli, in order to highlight which factors might alter TMPRSS2 expression, and thus impact the susceptibility to infection and COVID-19 prognosis. Moreover, we reported TMPRSS2 polymorphisms affecting its expression and suggested the ethnic groups more prone to COVID-19. Finally, we also highlighted a gender-specific co-expression between TMPRSS2 and other genes related to SARS-CoV-2 entry, maybe explaining the higher observed susceptibility of infection in men. Our results could be useful in designing potential prevention and treatment strategies regarding the COVID-19. Keywords COVID-19 . TMPRSS2 . Age . Co-expression . Gender
Introduction The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is rapidly spreading worldwide. In fact, as of October 2020, over 1 million deaths and 37 million positive cases have been reported globally [1]. Spike protein 3D structures of severe acute respiratory syndrome-coronavirus (SARS-CoV), responsible for the 2003 outbreak, and of the current SARS-CoV-2, resulted to be sufficiently similar to interact with the same host cell targets [2]. Indeed, recent studies reported the involvement of angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) also in SARS-CoV-2 infection [3]. Specifically, virus entry through the cell surface receptor ACE2 requires proteolytic cleavage and activation of the spike proteins by TMPRSS2 protease. Accordingly, the TMPRSS2 inhibitor
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s10096-02004089-y. * Francesco Piva [email protected] 1
Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, Italy
camostat mesylate blocked SARS-CoV-2 entry and might represent a treatment option [3].
Analysis of TMPRSS2 expression data Recent epidemiological data indicate that COVID-19 showed higher rates of critical illness and deaths in men, in smokers, in diabetics and in older people [4–7]. TMPRSS2 is mainly expressed in the lung, salivary gland, thyroid, gastrointestinal tract, pancreas, kidney and liver, according to RNA and protein expression data available at Human Protein Atlas (HPA) database (Fig. 1). Notably, it is also expressed in many male tissues, such as ductus deferens, epididymis, seminal vesicle and prostate, but it has very low expression, or it is absent in the testis and in all female tiss
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