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Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases
Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 20...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394573/ https://www.ncbi.nlm.nih.gov/pubmed/34440210 http://dx.doi.org/10.3390/biomedicines9081006 |
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author | Hattori, Toshio Iwasaki-Hozumi, Hiroko Bai, Gaowa Chagan-Yasutan, Haorile Shete, Ashwnini Telan, Elizabeth Freda Takahashi, Atsushi Ashino, Yugo Matsuba, Takashi |
author_facet | Hattori, Toshio Iwasaki-Hozumi, Hiroko Bai, Gaowa Chagan-Yasutan, Haorile Shete, Ashwnini Telan, Elizabeth Freda Takahashi, Atsushi Ashino, Yugo Matsuba, Takashi |
author_sort | Hattori, Toshio |
collection | PubMed |
description | Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg(168) [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg(168) from OPN-R to OPN-Leu(167) (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases. |
format | Online Article Text |
id | pubmed-8394573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83945732021-08-28 Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases Hattori, Toshio Iwasaki-Hozumi, Hiroko Bai, Gaowa Chagan-Yasutan, Haorile Shete, Ashwnini Telan, Elizabeth Freda Takahashi, Atsushi Ashino, Yugo Matsuba, Takashi Biomedicines Review Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg(168) [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg(168) from OPN-R to OPN-Leu(167) (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases. MDPI 2021-08-13 /pmc/articles/PMC8394573/ /pubmed/34440210 http://dx.doi.org/10.3390/biomedicines9081006 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Hattori, Toshio Iwasaki-Hozumi, Hiroko Bai, Gaowa Chagan-Yasutan, Haorile Shete, Ashwnini Telan, Elizabeth Freda Takahashi, Atsushi Ashino, Yugo Matsuba, Takashi Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases |
title | Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases |
title_full | Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases |
title_fullStr | Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases |
title_full_unstemmed | Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases |
title_short | Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases |
title_sort | both full-length and protease-cleaved products of osteopontin are elevated in infectious diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394573/ https://www.ncbi.nlm.nih.gov/pubmed/34440210 http://dx.doi.org/10.3390/biomedicines9081006 |
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