Dataset Information

SARS-CoV-2 infection causes periodontal fibrotic pathogenesis through deregulating mitochondrial beta-oxidation

ABSTRACT: The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus has four kinds of structural protein components: the spike protein, envelope protein, membrane protein, and nucleocapsid protein. SARS-CoV-2 virus mutate predominantly in the spike proteins, whilst the other key viral components remain stable. Essentially the pathological functions of the SARS-CoV-2 virus on different cell types are still largely unknown. Previous studies have shown that the human oral cavity can potentially act as reservoir of the SARS-CoV-2 virus. However, the consequence of SARS-CoV-2 viral infection on human oral health has not been systematically examined. COVID-19 can cause severe oral mucosa lesions and is likely to be connected with poor periodontal conditions. Fibroblasts are the key component of periodontal ligament (PDL) and express the SARS-CoV-2 receptor: Angiotensin-converting enzyme 2 (ACE2), whose expression level can increase upon bacterial infection hence potentially provide a direct route of SARS-CoV-2 infection to PDL fibroblasts. In this research, we aimed to study the pathogenicity of SARS-CoV-2 viral components on human fibroblasts. We found that by exposing to SARS-CoV-2, especially to the viral envelope and membrane proteins, the human periodontal fibroblasts could develop fibrotic pathogenic phenotypes, including hyperproliferation that was concomitant induced together with increased apoptosis and senescence. The fibrotic degeneration was mediated by a down-regulation of mitochondrial -oxidation in the fibroblasts. Fatty acid -oxidation inhibitor, etomoxir treatment could mirror the same pathological consequence on the cells, similar to SARS-CoV-2 infection. Our results therefore provide novel mechanistic insights into how SARS-CoV-2 infection can affect human periodontal health at the cell and molecular level with potential new therapeutic targets for COVID-19 induced fibrosis.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Gingival Epithelial Cell

DISEASE(S): Periodontitis

SUBMITTER: Vikram Sharma

LAB HEAD: Vikram Sharma

PROVIDER: PXD041281 | Pride | 2023-07-20

REPOSITORIES: Pride

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SARS-CoV-2 infection causes periodontal fibrotic pathogenesis through deregulating mitochondrial beta-oxidation.

Gao Yan Y Kok Wai Ling WL Sharma Vikram V Illsley Charlotte Sara CS Hanks Sally S Tredwin Christopher C Hu Bing B

Cell death discovery 20230526 1

The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus has four structural protein components: the spike protein, envelope protein, membrane protein, and nucleocapsid protein. The SARS-CoV-2 virus mutates predominantly in the spike proteins, whilst the other key viral components usually remain stable. Essentially the pathological functions of the SARS-CoV-2 virus on different cell types are still largely unknown. Previous studies have ...[more]

PMID: 37236979

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