Exosomes from COVID-19 Patients Carry Tenascin-C and Fibrinogen-β in Triggering Inflammatory Signals in Cells of Distant Organ |
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Authors: | Subhayan Sur Mousumi Khatun Robert Steele T. Scott Isbell Ranjit Ray Ratna B. Ray |
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Affiliation: | 1.Department of Pathology, Saint Louis University, St. Louis, MO 63104, USA; (S.S.); (M.K.); (R.S.); (T.S.I.);2.Department of Internal Medicine, Saint Louis University, St. Louis, MO 63104, USA; |
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Abstract: | SARS-CoV-2 infection can cause cytokine storm and may overshoot immunity in humans; however, it remains to be determined whether virus-induced soluble mediators from infected cells are carried by exosomes as vehicles to distant organs and cause tissue damage in COVID-19 patients. We took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and COVID-19 patients. Our results revealed that tenascin-C (TNC) and fibrinogen-β (FGB) are highly abundant in exosomes from COVID-19 patients’ plasma compared with that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via the Nuclear factor-κB (NF-κB) pathway, we examined the status of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C–C motif chemokine ligand 5 (CCL5) expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase compared with that from healthy subjects. Together, our results demonstrate that TNC and FGB are transported through plasma exosomes and potentially trigger pro-inflammatory cytokine signaling in cells of distant organ. |
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Keywords: | COVID-19, exosomes, mass spectrometry, tenascin-C, fibrinogen-β , cytokines, pathogenesis |
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