Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation
Summary: Lymphatic vessels are required for the clearance of excess fluid and immune cells from inflamed tissue, making the regulation of lymphangiogenesis an important area of research. Although the positive regulatory mechanisms of lymphangiogenesis are well known, the negative regulatory mechanis...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422500015X |
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| author | Daisuke Katoh Yoshiyuki Senga Kento Mizutani Kazuaki Maruyama Daishi Yamakawa Tadashi Yamamuro Michiaki Hiroe Keiichi Yamanaka Akihiro Sudo Naoyuki Katayama Toshimichi Yoshida Kyoko Imanaka-Yoshida |
| author_facet | Daisuke Katoh Yoshiyuki Senga Kento Mizutani Kazuaki Maruyama Daishi Yamakawa Tadashi Yamamuro Michiaki Hiroe Keiichi Yamanaka Akihiro Sudo Naoyuki Katayama Toshimichi Yoshida Kyoko Imanaka-Yoshida |
| author_sort | Daisuke Katoh |
| collection | DOAJ |
| description | Summary: Lymphatic vessels are required for the clearance of excess fluid and immune cells from inflamed tissue, making the regulation of lymphangiogenesis an important area of research. Although the positive regulatory mechanisms of lymphangiogenesis are well known, the negative regulatory mechanisms observed during inflammation remain unclear. Here, we identify tenascin-C (TNC) as a spatiotemporal negative regulator of lymphangiogenesis during inflammation. We found an inverse correlation between lymphangiogenesis and TNC expression in a mouse lymphedema model. Genetic deletion of Tnc promotes lymphangiogenesis and improves lymphatic drainage function, thereby accelerating the resolution of inflammation. Conversely, the exogenous addition of TNC suppresses lymphangiogenesis and prolongs inflammation. TNC inhibits the proliferation and promotes apoptosis of lymphatic endothelial cells. Mechanistically, TNC facilitates integrin αvβ1 heterodimer formation, leading to the activation of non-canonical (TAK1/p38MAPK/ATF-2) TGFβ signaling to suppress lymphangiogenesis. Our study highlights the importance of negative regulation of lymphangiogenesis in modulating immune responses. |
| format | Article |
| id | doaj-art-b5fbe0be0e6a40f1944f67c66e248496 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-b5fbe0be0e6a40f1944f67c66e2484962025-01-26T05:04:34ZengElsevieriScience2589-00422025-02-01282111756Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammationDaisuke Katoh0Yoshiyuki Senga1Kento Mizutani2Kazuaki Maruyama3Daishi Yamakawa4Tadashi Yamamuro5Michiaki Hiroe6Keiichi Yamanaka7Akihiro Sudo8Naoyuki Katayama9Toshimichi Yoshida10Kyoko Imanaka-Yoshida11Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie, Japan; Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Corresponding authorDepartment of Orthopedic Surgery, Mie University Graduate School of Medicine, Tsu, Mie, JapanDepartment of Dermatology, Mie University Graduate School of Medicine, Tsu, Mie, JapanDepartment of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie, JapanDepartment of Physiology, Mie University Graduate School of Medicine, Tsu, Mie, JapanDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USADepartment of Cardiology, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, JapanDepartment of Dermatology, Mie University Graduate School of Medicine, Tsu, Mie, JapanDepartment of Orthopedic Surgery, Mie University Graduate School of Medicine, Tsu, Mie, JapanDepartment of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, JapanDepartment of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie, JapanDepartment of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie, JapanSummary: Lymphatic vessels are required for the clearance of excess fluid and immune cells from inflamed tissue, making the regulation of lymphangiogenesis an important area of research. Although the positive regulatory mechanisms of lymphangiogenesis are well known, the negative regulatory mechanisms observed during inflammation remain unclear. Here, we identify tenascin-C (TNC) as a spatiotemporal negative regulator of lymphangiogenesis during inflammation. We found an inverse correlation between lymphangiogenesis and TNC expression in a mouse lymphedema model. Genetic deletion of Tnc promotes lymphangiogenesis and improves lymphatic drainage function, thereby accelerating the resolution of inflammation. Conversely, the exogenous addition of TNC suppresses lymphangiogenesis and prolongs inflammation. TNC inhibits the proliferation and promotes apoptosis of lymphatic endothelial cells. Mechanistically, TNC facilitates integrin αvβ1 heterodimer formation, leading to the activation of non-canonical (TAK1/p38MAPK/ATF-2) TGFβ signaling to suppress lymphangiogenesis. Our study highlights the importance of negative regulation of lymphangiogenesis in modulating immune responses.http://www.sciencedirect.com/science/article/pii/S258900422500015XNatural sciencesBiological sciencesImmunology |
| spellingShingle | Daisuke Katoh Yoshiyuki Senga Kento Mizutani Kazuaki Maruyama Daishi Yamakawa Tadashi Yamamuro Michiaki Hiroe Keiichi Yamanaka Akihiro Sudo Naoyuki Katayama Toshimichi Yoshida Kyoko Imanaka-Yoshida Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation iScience Natural sciences Biological sciences Immunology |
| title | Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation |
| title_full | Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation |
| title_fullStr | Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation |
| title_full_unstemmed | Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation |
| title_short | Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation |
| title_sort | negative regulation of lymphangiogenesis by tenascin c delays the resolution of inflammation |
| topic | Natural sciences Biological sciences Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422500015X |
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