Evidence map›Paper›PMID 39865553›Full record

ArticleBioFactors (Oxford, England)

Involvement of metformin and aging in salivary expression of ACE2 and TMPRSS2.

Yosuke Shikama, Kunihiro Otsuka, Yuka Shikama, Masae Furukawa, Naozumi Ishimaru, Kenji Matsushita

Abstract read
In one paragraph

Article in BioFactors (Oxford, England). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
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  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Yosuke ShikamaDepartment of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Japan.ORCID https://orcid.org/0000-0002-0495-8393
Kunihiro OtsukaDepartment of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.ORCID https://orcid.org/0000-0002-3546-8143
Yuka ShikamaDepartment of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Japan.
Masae FurukawaDepartment of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Japan.
Naozumi IshimaruDepartment of Oral Pathology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Kenji MatsushitaDepartment of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Japan.

Funding

Japan Society for the Promotion of Science 21H03115Research Funding for Longevity Sciences from the National Center for Geriatrics and Gerontology 21-6Research Funding for Longevity Sciences from the National Center for Geriatrics and Gerontology 24-4
6 · The paper itself

Abstract

SARS-CoV-2-related proteins, ACE2 and TMPRSS2, are determinants of SARS-CoV-2 infection. Although these proteins are expressed in oral-related tissues, their expression patterns and modulatory mechanisms in the salivary glands remain unknown. We herein showed that full-length ACE2, which has both a fully functional enzyme catalytic site and high-affinity SARS-CoV-2 spike S1-binding sites, was more highly expressed in salivary glands than in oral mucosal epithelial cells and the lungs. Regarding TMPRSS2, zymogen and the cleaved form were both expressed in the salivary glands, whereas only zymogen was expressed in murine lacrimal glands and the lungs. Metformin, an AMPK activator, increased stimulated saliva secretion and full-length ACE2 expression and decreased cleaved TMPRSS2 expression in the salivary glands, and exerted the same effects on soluble ACE2 (sACE2) and sTMPRSS2 in saliva. Moreover, metformin decreased the expression of beta-galactosidase, a senescence marker, and ADAM17, a sheddase of ACE2 to sACE2, in the salivary glands. In aged mice, the expression of ACE2 was decreased in the salivary glands, whereas that of sACE2 was increased in saliva, presumably by the up-regulated expression of ADAM17. The expression of TMPRSS2 in the salivary glands and sTMPRSS2 in saliva were both increased. Collectively, these results suggest that the protein expression patterns of ACE2 and TMPRSS2 in the salivary glands differ from those in other oral-related cells and tissues, and also that metformin and aging affect the salivary expression of ACE2 and TMPRSS2, which have the potential as targets for preventing the transmission of SARS-CoV-2.

Indexed as

AgingAngiotensin-Converting Enzyme 2MetforminSalivaSalivary GlandsSerine EndopeptidasesADAM17 ProteinAnimalsCOVID-19HumansMaleMiceMice, Inbred C57BLMouth MucosaSARS-CoV-2ACE2 protein, humanAce2 protein, mouseADAM17 ProteinAdam17 protein, mouseAngiotensin-Converting Enzyme 2MetforminSerine EndopeptidasesTMPRSS2 protein, humanTMPRSS2 protein, mouseADAM17epithelial cellssalivasalivary glandsSARS‐CoV‐2

Identifiers

PMID39865553
PMCPMC11771682

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.