Browsing by Subject "ACE2"

Now showing 1 - 2 of 2
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    Sex, androgens and regulation of pulmonary AR, TMPRSS2 and ACE2
    (Cold Spring Harbor Laboratory, 2020-10-14) Baratchian, Mehdi; McManus, Jeffrey M.; Berk, Mike; Nakamura, Fumihiko; Mukhopadhyay, Sanjay; Xu, Weiling; Erzurum, Serpil; Drazba, Judy; Peterson, John; Klein, Eric A.; Gaston, Ben; Sharifi, Nima; Pediatrics, School of Medicine
    The sex discordance in COVID-19 outcomes has been widely recognized, with males generally faring worse than females and a potential link to sex steroids. A plausible mechanism is androgen-induced expression of TMPRSS2 and/or ACE2 in pulmonary tissues that may increase susceptibility or severity in males. This hypothesis is the subject of several clinical trials of anti-androgen therapies around the world. Here, we investigated the sex-associated TMPRSS2 and ACE2 expression in human and mouse lungs and interrogated the possibility of pharmacologic modification of their expression with anti-androgens. We found no evidence for increased TMPRSS2 expression in the lungs of males compared to females in humans or mice. Furthermore, in male mice, treatment with the androgen receptor antagonist enzalutamide did not decrease pulmonary TMPRSS2. On the other hand, ACE2 and AR expression was sexually dimorphic and higher in males than females. ACE2 was moderately suppressible with enzalutamide therapy. Our work suggests that sex differences in COVID-19 outcomes attributable to viral entry are independent of TMPRSS2. Modest changes in ACE2 could account for some of the sex discordance.
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    Type 2 Immunity and Age Modify Gene Expression of COVID19 Receptors in Eosinophilic Gastrointestinal Disorders
    (Wolters Kluwer, 2020-12) Chiang, Austin W. T.; Duong, Loan D.; Shoda, Tetsuo; Nhu, Quan M.; Ruffner, Melanie; Hara, Takeo; Aaron, Bailey; Joplin, Erik; Manresa, Mario; Abonia, J. Pablo; Dellon, Evan; Hirano, Ikuo; Gonsalves, Nirmala; Gupta, Sandeep; Furuta, Glenn; Rothenberg, Marc E.; Lewis, Nathan E.; Muir, Amanda B.; Aceves, Seema S.; Medicine, School of Medicine
    Infection with SARS-CoV-2 can lead to COVID-19. The gastrointestinal tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin converting enzyme-2 (ACE2) and the serine protease TMPRSS2. Eosinophilic gastrointestinal disorders are inflammatory conditions caused by chronic type 2 (T2) inflammation. However, the effects of the T2 atopic inflammatory milieu on SARS-COV-2 viral entry gene expression in the GI tract is poorly understood. We analyzed tissue ACE2 and TMPRSS2 gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG) and in normal adult esophagi using publicly available RNA sequencing datasets. Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared to control non-EoE/EG esophagus/stomach. ACE2 gene expression was significantly lower in esophagi from children with or without EoE and from adults with EoE as compared to normal adult esophagi. Type 2 immunity and pediatric age could be protective for infection by SARS-CoV-2 in the gastrointestinal tract due to decreased expression of ACE2.