Macrophages promote Fibrinogenesis during kidney injury
Macrophages (Mø) are widely considered fundamental in the development of kidney fibrosis since Mø accumulation commonly aggravates kidney fibrosis, while Mø depletion mitigates it. Although many studies have aimed to elucidate Mø-dependent mechanisms linked to kidney fibrosis and have suggested vari...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1206362/full |
| _version_ | 1797797718860496896 |
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| author | Hanna Oh Hanna Oh Ohbin Kwon Ohbin Kwon Min Jung Kong Kwon Moo Park Jea-Hyun Baek Jea-Hyun Baek |
| author_facet | Hanna Oh Hanna Oh Ohbin Kwon Ohbin Kwon Min Jung Kong Kwon Moo Park Jea-Hyun Baek Jea-Hyun Baek |
| author_sort | Hanna Oh |
| collection | DOAJ |
| description | Macrophages (Mø) are widely considered fundamental in the development of kidney fibrosis since Mø accumulation commonly aggravates kidney fibrosis, while Mø depletion mitigates it. Although many studies have aimed to elucidate Mø-dependent mechanisms linked to kidney fibrosis and have suggested various mechanisms, the proposed roles have been mostly passive, indirect, and non-unique to Mø. Therefore, the molecular mechanism of how Mø directly promote kidney fibrosis is not fully understood. Recent evidence suggests that Mø produce coagulation factors under diverse pathologic conditions. Notably, coagulation factors mediate fibrinogenesis and contribute to fibrosis. Thus, we hypothesized that kidney Mø express coagulation factors that contribute to the provisional matrix formation during acute kidney injury (AKI). To test our hypothesis, we probed for Mø-derived coagulation factors after kidney injury and uncovered that both infiltrating and kidney-resident Mø produce non-redundant coagulation factors in AKI and chronic kidney disease (CKD). We also identified F13a1, which catalyzes the final step of the coagulation cascade, as the most strongly upregulated coagulation factor in murine and human kidney Mø during AKI and CKD. Our in vitro experiments revealed that the upregulation of coagulation factors in Mø occurs in a Ca2 + −dependent manner. Taken together, our study demonstrates that kidney Mø populations express key coagulation factors following local injury, suggesting a novel effector mechanism of Mø contributing to kidney fibrosis. |
| first_indexed | 2024-03-13T03:52:37Z |
| format | Article |
| id | doaj.art-2ff72db753c04a73849332f1db2970aa |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-13T03:52:37Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-2ff72db753c04a73849332f1db2970aa2023-06-22T09:37:38ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-06-011010.3389/fmed.2023.12063621206362Macrophages promote Fibrinogenesis during kidney injuryHanna Oh0Hanna Oh1Ohbin Kwon2Ohbin Kwon3Min Jung Kong4Kwon Moo Park5Jea-Hyun Baek6Jea-Hyun Baek7Laboratory of Inflammation Research, Handong Global University, Pohang, Gyeongbuk, South KoreaSchool of Life Science, Handong Global University, Pohang, Gyeongbuk, South KoreaLaboratory of Inflammation Research, Handong Global University, Pohang, Gyeongbuk, South KoreaSchool of Life Science, Handong Global University, Pohang, Gyeongbuk, South KoreaDepartment of Anatomy, BK21Plus, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, South KoreaDepartment of Anatomy, BK21Plus, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu, South KoreaLaboratory of Inflammation Research, Handong Global University, Pohang, Gyeongbuk, South KoreaSchool of Life Science, Handong Global University, Pohang, Gyeongbuk, South KoreaMacrophages (Mø) are widely considered fundamental in the development of kidney fibrosis since Mø accumulation commonly aggravates kidney fibrosis, while Mø depletion mitigates it. Although many studies have aimed to elucidate Mø-dependent mechanisms linked to kidney fibrosis and have suggested various mechanisms, the proposed roles have been mostly passive, indirect, and non-unique to Mø. Therefore, the molecular mechanism of how Mø directly promote kidney fibrosis is not fully understood. Recent evidence suggests that Mø produce coagulation factors under diverse pathologic conditions. Notably, coagulation factors mediate fibrinogenesis and contribute to fibrosis. Thus, we hypothesized that kidney Mø express coagulation factors that contribute to the provisional matrix formation during acute kidney injury (AKI). To test our hypothesis, we probed for Mø-derived coagulation factors after kidney injury and uncovered that both infiltrating and kidney-resident Mø produce non-redundant coagulation factors in AKI and chronic kidney disease (CKD). We also identified F13a1, which catalyzes the final step of the coagulation cascade, as the most strongly upregulated coagulation factor in murine and human kidney Mø during AKI and CKD. Our in vitro experiments revealed that the upregulation of coagulation factors in Mø occurs in a Ca2 + −dependent manner. Taken together, our study demonstrates that kidney Mø populations express key coagulation factors following local injury, suggesting a novel effector mechanism of Mø contributing to kidney fibrosis.https://www.frontiersin.org/articles/10.3389/fmed.2023.1206362/fullkidney fibrosischronic kidney diseasemacrophagescoagulation factorfibrinogenesis |
| spellingShingle | Hanna Oh Hanna Oh Ohbin Kwon Ohbin Kwon Min Jung Kong Kwon Moo Park Jea-Hyun Baek Jea-Hyun Baek Macrophages promote Fibrinogenesis during kidney injury Frontiers in Medicine kidney fibrosis chronic kidney disease macrophages coagulation factor fibrinogenesis |
| title | Macrophages promote Fibrinogenesis during kidney injury |
| title_full | Macrophages promote Fibrinogenesis during kidney injury |
| title_fullStr | Macrophages promote Fibrinogenesis during kidney injury |
| title_full_unstemmed | Macrophages promote Fibrinogenesis during kidney injury |
| title_short | Macrophages promote Fibrinogenesis during kidney injury |
| title_sort | macrophages promote fibrinogenesis during kidney injury |
| topic | kidney fibrosis chronic kidney disease macrophages coagulation factor fibrinogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1206362/full |
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