Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a  murine model of deep vein thrombosis

Abstract Heat shock proteins (HSPs) are molecular chaperones whose primary function is cytoprotection, supporting cell survival under (sub) lethal conditions. They have been implicated in various diseases such as inflammatory diseases and cancer due to their cytoprotective and immunomodulatory effec...

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Main Authors: Mizuho Nosaka, Yuko Ishida, Yumi Kuninaka, Akiko Ishigami, Akira Taruya, Emi Shimada, Yumiko Hashizume, Hiroki Yamamoto, Akihiko Kimura, Fukumi Furukawa, Toshikazu Kondo
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-48987-5
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author Mizuho Nosaka
Yuko Ishida
Yumi Kuninaka
Akiko Ishigami
Akira Taruya
Emi Shimada
Yumiko Hashizume
Hiroki Yamamoto
Akihiko Kimura
Fukumi Furukawa
Toshikazu Kondo
author_facet Mizuho Nosaka
Yuko Ishida
Yumi Kuninaka
Akiko Ishigami
Akira Taruya
Emi Shimada
Yumiko Hashizume
Hiroki Yamamoto
Akihiko Kimura
Fukumi Furukawa
Toshikazu Kondo
author_sort Mizuho Nosaka
collection DOAJ
description Abstract Heat shock proteins (HSPs) are molecular chaperones whose primary function is cytoprotection, supporting cell survival under (sub) lethal conditions. They have been implicated in various diseases such as inflammatory diseases and cancer due to their cytoprotective and immunomodulatory effects, and their biological mechanisms have been studied. Central family members include, HSP27, which is induced by various stimuli such as heat shock, hypoxia, hyperoxia, ultraviolet exposure, and nutritional deficiency, and HSP70, which is homeostatically expressed in many organs such as the gastrointestinal tract and has anti-cell death and anti-inflammatory effects. In this study, HSP27 and HSP70 were investigated during thrombus formation and dissolution in a deep vein thrombosis model by immunohistochemistry to determine their involvement in this process and whether their expression could be used as a forensic marker. In the process of thrombus formation and lysis, HSP27 and HSP70 were found to be expressed by immunohistochemical analysis. The role of inhibitors of HSP27 and HSP70 in the pathogenesis of thrombosis in mice was also investigated. When HSP27 or HSP70 inhibitors were administered, thrombi were significantly smaller than in the control group on day 5 after inferior vena cava ligation, indicating pro-thrombotic effects HSP27 and HSP70. If HSP27- or HSP70-positive cells were clearly visible and easily identifiable in the thrombus sections, the thrombus was presumed to be more than 10 days old. Thus, the detection of intrathrombotic HSP27 and HSP70 could forensically provide useful information for the estimation of thrombus ages. Collectively, our study implied that both HSP27 and HSP70 might be molecular targets for thrombus therapy and that the detection of HSP-related molecules such as HSP27 and HSP70 could be useful for the determination of thrombus ages.
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spelling doaj.art-f15d2c454c55432c9fec69985b1deb2a2023-12-17T12:12:57ZengNature PortfolioScientific Reports2045-23222023-12-0113111110.1038/s41598-023-48987-5Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a  murine model of deep vein thrombosisMizuho Nosaka0Yuko Ishida1Yumi Kuninaka2Akiko Ishigami3Akira Taruya4Emi Shimada5Yumiko Hashizume6Hiroki Yamamoto7Akihiko Kimura8Fukumi Furukawa9Toshikazu Kondo10Department of Forensic Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityDepartment of Cardiovascular Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityDepartment of Forensic Medicine, Wakayama Medical UniversityAbstract Heat shock proteins (HSPs) are molecular chaperones whose primary function is cytoprotection, supporting cell survival under (sub) lethal conditions. They have been implicated in various diseases such as inflammatory diseases and cancer due to their cytoprotective and immunomodulatory effects, and their biological mechanisms have been studied. Central family members include, HSP27, which is induced by various stimuli such as heat shock, hypoxia, hyperoxia, ultraviolet exposure, and nutritional deficiency, and HSP70, which is homeostatically expressed in many organs such as the gastrointestinal tract and has anti-cell death and anti-inflammatory effects. In this study, HSP27 and HSP70 were investigated during thrombus formation and dissolution in a deep vein thrombosis model by immunohistochemistry to determine their involvement in this process and whether their expression could be used as a forensic marker. In the process of thrombus formation and lysis, HSP27 and HSP70 were found to be expressed by immunohistochemical analysis. The role of inhibitors of HSP27 and HSP70 in the pathogenesis of thrombosis in mice was also investigated. When HSP27 or HSP70 inhibitors were administered, thrombi were significantly smaller than in the control group on day 5 after inferior vena cava ligation, indicating pro-thrombotic effects HSP27 and HSP70. If HSP27- or HSP70-positive cells were clearly visible and easily identifiable in the thrombus sections, the thrombus was presumed to be more than 10 days old. Thus, the detection of intrathrombotic HSP27 and HSP70 could forensically provide useful information for the estimation of thrombus ages. Collectively, our study implied that both HSP27 and HSP70 might be molecular targets for thrombus therapy and that the detection of HSP-related molecules such as HSP27 and HSP70 could be useful for the determination of thrombus ages.https://doi.org/10.1038/s41598-023-48987-5
spellingShingle Mizuho Nosaka
Yuko Ishida
Yumi Kuninaka
Akiko Ishigami
Akira Taruya
Emi Shimada
Yumiko Hashizume
Hiroki Yamamoto
Akihiko Kimura
Fukumi Furukawa
Toshikazu Kondo
Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a  murine model of deep vein thrombosis
Scientific Reports
title Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a  murine model of deep vein thrombosis
title_full Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a  murine model of deep vein thrombosis
title_fullStr Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a  murine model of deep vein thrombosis
title_full_unstemmed Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a  murine model of deep vein thrombosis
title_short Relationship between intrathrombotic appearance of HSP27 and HSP70 and thrombus ages in a  murine model of deep vein thrombosis
title_sort relationship between intrathrombotic appearance of hsp27 and hsp70 and thrombus ages in a murine model of deep vein thrombosis
url https://doi.org/10.1038/s41598-023-48987-5
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