Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice
Abstract The liver has a high regenerative ability and can induce spontaneous regression of fibrosis when early liver damage occurs; however, these abilities are lost when chronic liver damage results in decompensated cirrhosis. Cell therapies, such as mesenchymal stem cell (MSC) and macrophage ther...
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Format: | Article |
Language: | English |
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BMC
2021-09-01
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Series: | Inflammation and Regeneration |
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Online Access: | https://doi.org/10.1186/s41232-021-00177-4 |
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doaj-b12286f4bc7841a399f9b7b2e8ece5b3 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shunsuke Nojiri Atsunori Tsuchiya Kazuki Natsui Suguru Takeuchi Takayuki Watanabe Yuichi Kojima Yusuke Watanabe Hiroteru Kamimura Masahiro Ogawa Satoko Motegi Takahiro Iwasawa Takeki Sato Masaru Kumagai Yui Ishii Tomomi Kitayama Yu-Tung Li Yuya Ouchi Takashi Shimbo Masaaki Takamura Katsuto Tamai Shuji Terai |
spellingShingle |
Shunsuke Nojiri Atsunori Tsuchiya Kazuki Natsui Suguru Takeuchi Takayuki Watanabe Yuichi Kojima Yusuke Watanabe Hiroteru Kamimura Masahiro Ogawa Satoko Motegi Takahiro Iwasawa Takeki Sato Masaru Kumagai Yui Ishii Tomomi Kitayama Yu-Tung Li Yuya Ouchi Takashi Shimbo Masaaki Takamura Katsuto Tamai Shuji Terai Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice Inflammation and Regeneration HMGB1 Peptide Liver Cirrhosis Fibrosis Mesenchymal stem cell |
author_facet |
Shunsuke Nojiri Atsunori Tsuchiya Kazuki Natsui Suguru Takeuchi Takayuki Watanabe Yuichi Kojima Yusuke Watanabe Hiroteru Kamimura Masahiro Ogawa Satoko Motegi Takahiro Iwasawa Takeki Sato Masaru Kumagai Yui Ishii Tomomi Kitayama Yu-Tung Li Yuya Ouchi Takashi Shimbo Masaaki Takamura Katsuto Tamai Shuji Terai |
author_sort |
Shunsuke Nojiri |
title |
Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice |
title_short |
Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice |
title_full |
Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice |
title_fullStr |
Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice |
title_full_unstemmed |
Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice |
title_sort |
synthesized hmgb1 peptide attenuates liver inflammation and suppresses fibrosis in mice |
publisher |
BMC |
series |
Inflammation and Regeneration |
issn |
1880-8190 |
publishDate |
2021-09-01 |
description |
Abstract The liver has a high regenerative ability and can induce spontaneous regression of fibrosis when early liver damage occurs; however, these abilities are lost when chronic liver damage results in decompensated cirrhosis. Cell therapies, such as mesenchymal stem cell (MSC) and macrophage therapies, have attracted attention as potential strategies for mitigating liver fibrosis. Here, we evaluated the therapeutic effects of HMGB1 peptide synthesized from box A of high mobility group box 1 protein. Liver damage and fibrosis were evaluated using a carbon tetrachloride (CCl4)-induced cirrhosis mouse model. The effects of HMGB1 peptide against immune cells were evaluated by single-cell RNA-seq using liver tissues, and those against monocytes/macrophages were further evaluated by in vitro analyses. Administration of HMGB1 peptide did not elicit a rapid response within 36 h, but attenuated liver damage after 1 week and suppressed fibrosis after 2 weeks. Fibrosis regression developed over time, despite continuous liver damage, suggesting that administration of this peptide could induce fibrolysis. In vitro analyses could not confirm a direct effect of HMGB1 peptide against monocyte/macrophages. However, macrophages were the most affected immune cells in the liver, and the number of scar-associated macrophages (Trem2+Cd9+ cells) with anti-inflammatory markers increased in the liver following HMGB1 treatment, suggesting that indirect effects of monocytes/macrophages were important for therapeutic efficacy. Overall, we established a new concept for cell-free therapy using HMGB1 peptide for cirrhosis through the induction of anti-inflammatory macrophages. |
topic |
HMGB1 Peptide Liver Cirrhosis Fibrosis Mesenchymal stem cell |
url |
https://doi.org/10.1186/s41232-021-00177-4 |
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doaj-b12286f4bc7841a399f9b7b2e8ece5b32021-10-03T11:42:19ZengBMCInflammation and Regeneration1880-81902021-09-0141111510.1186/s41232-021-00177-4Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in miceShunsuke Nojiri0Atsunori Tsuchiya1Kazuki Natsui2Suguru Takeuchi3Takayuki Watanabe4Yuichi Kojima5Yusuke Watanabe6Hiroteru Kamimura7Masahiro Ogawa8Satoko Motegi9Takahiro Iwasawa10Takeki Sato11Masaru Kumagai12Yui Ishii13Tomomi Kitayama14Yu-Tung Li15Yuya Ouchi16Takashi Shimbo17Masaaki Takamura18Katsuto Tamai19Shuji Terai20Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka UniversityDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka UniversityDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka UniversityDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka UniversityDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityAbstract The liver has a high regenerative ability and can induce spontaneous regression of fibrosis when early liver damage occurs; however, these abilities are lost when chronic liver damage results in decompensated cirrhosis. Cell therapies, such as mesenchymal stem cell (MSC) and macrophage therapies, have attracted attention as potential strategies for mitigating liver fibrosis. Here, we evaluated the therapeutic effects of HMGB1 peptide synthesized from box A of high mobility group box 1 protein. Liver damage and fibrosis were evaluated using a carbon tetrachloride (CCl4)-induced cirrhosis mouse model. The effects of HMGB1 peptide against immune cells were evaluated by single-cell RNA-seq using liver tissues, and those against monocytes/macrophages were further evaluated by in vitro analyses. Administration of HMGB1 peptide did not elicit a rapid response within 36 h, but attenuated liver damage after 1 week and suppressed fibrosis after 2 weeks. Fibrosis regression developed over time, despite continuous liver damage, suggesting that administration of this peptide could induce fibrolysis. In vitro analyses could not confirm a direct effect of HMGB1 peptide against monocyte/macrophages. However, macrophages were the most affected immune cells in the liver, and the number of scar-associated macrophages (Trem2+Cd9+ cells) with anti-inflammatory markers increased in the liver following HMGB1 treatment, suggesting that indirect effects of monocytes/macrophages were important for therapeutic efficacy. Overall, we established a new concept for cell-free therapy using HMGB1 peptide for cirrhosis through the induction of anti-inflammatory macrophages.https://doi.org/10.1186/s41232-021-00177-4HMGB1PeptideLiverCirrhosisFibrosisMesenchymal stem cell |