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, <i>Mycobacterium tuberculosis</i> (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and cor...
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MDPI AG
2021-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/8/1006 |
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| author | Toshio Hattori Hiroko Iwasaki-Hozumi Gaowa Bai Haorile Chagan-Yasutan Ashwnini Shete Elizabeth Freda Telan Atsushi Takahashi Yugo Ashino Takashi Matsuba |
| author_facet | Toshio Hattori Hiroko Iwasaki-Hozumi Gaowa Bai Haorile Chagan-Yasutan Ashwnini Shete Elizabeth Freda Telan Atsushi Takahashi Yugo Ashino Takashi Matsuba |
| author_sort | Toshio Hattori |
| collection | DOAJ |
| description | Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, <i>Mycobacterium tuberculosis</i> (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<sup>168</sup> [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg<sup>168</sup> from OPN-R to OPN-Leu<sup>167</sup> (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. |
| first_indexed | 2024-03-10T08:59:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T08:59:17Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-3f794632ecac49509464cef8e5f09b232023-11-22T06:53:15ZengMDPI AGBiomedicines2227-90592021-08-0198100610.3390/biomedicines9081006Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious DiseasesToshio Hattori0Hiroko Iwasaki-Hozumi1Gaowa Bai2Haorile Chagan-Yasutan3Ashwnini Shete4Elizabeth Freda Telan5Atsushi Takahashi6Yugo Ashino7Takashi Matsuba8Research Institute of Health and Welfare, Kibi International University, Takahashi 716-8508, JapanResearch Institute of Health and Welfare, Kibi International University, Takahashi 716-8508, JapanResearch Institute of Health and Welfare, Kibi International University, Takahashi 716-8508, JapanResearch Institute of Health and Welfare, Kibi International University, Takahashi 716-8508, JapanICMR-National AIDS Research Institute, 73 G-Block, MIDC, Bhosari, Pune 411026, IndiaSTD AIDS Cooperative Central Laboratory, San Lazaro Hospital, Manila 1003, PhilippinesResearch Institute of Health and Welfare, Kibi International University, Takahashi 716-8508, JapanDepartment of Respiratory Medicine, Sendai City Hospital, Sendai 982-8502, JapanDepartment of Animal Pharmaceutical Science, School of Pharmaceutical Science, Kyusyu University of Health and Welfare, Nobeoka 882-8508, JapanCirculating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, <i>Mycobacterium tuberculosis</i> (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<sup>168</sup> [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg<sup>168</sup> from OPN-R to OPN-Leu<sup>167</sup> (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.https://www.mdpi.com/2227-9059/9/8/1006osteopontininfectious diseasetuberculosisadult T-cell leukemiahuman immunodeficiency virusdengue virus |
| spellingShingle | Toshio Hattori Hiroko Iwasaki-Hozumi Gaowa Bai Haorile Chagan-Yasutan Ashwnini Shete Elizabeth Freda Telan Atsushi Takahashi Yugo Ashino Takashi Matsuba Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases Biomedicines osteopontin infectious disease tuberculosis adult T-cell leukemia human immunodeficiency virus dengue virus |
| 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 | osteopontin infectious disease tuberculosis adult T-cell leukemia human immunodeficiency virus dengue virus |
| url | https://www.mdpi.com/2227-9059/9/8/1006 |
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