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Updated: Jul 24, 2025

Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry
Published on: October 18, 2016
Macrophages promote Fibrinogenesis during kidney injury
Hanna Oh1,2, Ohbin Kwon1,2, Min Jung Kong3
1Laboratory of Inflammation Research, Handong Global University, Pohang, Gyeongbuk, South Korea.
Abstract:
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.
Insights
Macrophages promote kidney fibrosis by producing coagulation factors, including F13a1, a key enzyme in the coagulation cascade. This study reveals a novel mechanism for macrophage-driven kidney fibrosis.
Area of Science:
- Nephrology
- Immunology
- Hematology
Background:
- Macrophages are crucial in kidney fibrosis development.
- Existing knowledge on macrophage roles in fibrosis is limited and often indirect.
- The direct molecular mechanisms by which macrophages promote kidney fibrosis remain unclear.
Purpose of the Study:
- To investigate the hypothesis that kidney macrophages express coagulation factors contributing to kidney fibrosis.
- To identify specific coagulation factors produced by macrophages in kidney injury models.
- To elucidate the role of macrophage-derived coagulation factors in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease (CKD).
Main Methods:
- Probing for macrophage-derived coagulation factors in kidney injury models.
- Analyzing both infiltrating and resident kidney macrophages.
- Utilizing murine and human kidney samples from AKI and CKD patients.
- Performing in vitro experiments to assess calcium-dependent upregulation of coagulation factors.
Main Results:
- Both infiltrating and kidney-resident macrophages produce distinct coagulation factors in AKI and CKD.
- Factor F13a1, crucial for the terminal coagulation cascade, showed significant upregulation in kidney macrophages during AKI and CKD.
- In vitro studies confirmed that calcium ions regulate the expression of coagulation factors in macrophages.
Conclusions:
- Kidney macrophages express key coagulation factors following injury.
- Macrophage-derived coagulation factors represent a novel mechanism contributing to kidney fibrosis.
- Targeting these factors may offer new therapeutic strategies for kidney fibrosis.
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