Expression of ACE2 and TMPRSS2 Proteins in the Upper and Lower Aerodigestive Tracts of Rats: Implications on COVID 19 Infections

  1. Taku Sato
  2. Rumi Ueha
  3. Takao Goto
  4. Akihito Yamauchi
  5. Kenji Kondo
  6. Tatsuya Yamasoba

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Abstract

Patients with coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), exhibit not only respiratory symptoms but also symptoms of chemo‐sensitive disorders. Cellular entry of SARS‐CoV‐2 depends on the binding of its spike protein to a cellular receptor named angiotensin‐converting enzyme 2 (ACE2), and the subsequent spike protein‐priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS‐CoV‐2.

Methods

To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS‐CoV‐2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats.

Results

Co‐expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. Remarkably, TMPRSS2 expression was more distinct in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID‐19, such as the loss of taste, loss of olfaction, and respiratory dysfunction.

Conclusions

A wide range of organs have been speculated to be affected by SARS‐CoV‐2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID‐19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID‐19.

Level of Evidence

NA Laryngoscope , 131:E932–E939, 2021

Article activity feed

  1. Version published to 10.1002/lary.29132
  2. ScreenIT

    SciScore for 10.1101/2020.05.14.097204: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All animal experiments were conducted in accordance with institutional guidelines and with the approval of the Animal Care and Use Committee of the University of Tokyo (No. P14-051, P17-126).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableFive eight-week-old male Sprague Dawley rats were included in the control group.

    Table 2: Resources

    Antibodies
    SentencesResources
    After antibody activation, primary antibodies against ACE2 (1:300 dilution; rabbit monoclonal, Abcam, ab108252; Cambridge, UK) and TMPRSS2 (1:1000 dilution; rabbit monoclonal, Abcam, ab92323; Cambridge, UK) were detected with appropriate peroxidase-conjugated secondary antibodies and a diaminobenzidine substrate.
    ACE2
    suggested: (Abcam Cat# ab108252, RRID:AB_10864415)
    TMPRSS2
    suggested: (Abcam Cat# ab92323, RRID:AB_10585592)
    Experimental Models: Organisms/Strains
    SentencesResources
    Five eight-week-old male Sprague Dawley rats were included in the control group.
    Sprague Dawley
    suggested: RRID:RGD_737903)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    As for limitations of the present study, the evaluation was performed on young rats which may not correctly reflect the backgrounds of COVID-19 in human. Future clinical case studies and autopsy studies might strengthen this study.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.05.14.097204v1 on bioRxiv