Macrophages promote Fibrinogenesis during kidney injury

초록

Macrophages (Mo) are widely considered fundamental in the development of kidney fibrosis since Mo accumulation commonly aggravates kidney fibrosis, while Mo depletion mitigates it. Although many studies have aimed to elucidate Mo-dependent mechanisms linked to kidney fibrosis and have suggested various mechanisms, the proposed roles have been mostly passive, indirect, and non-unique to Mo. Therefore, the molecular mechanism of how Mo directly promote kidney fibrosis is not fully understood. Recent evidence suggests that Mo produce coagulation factors under diverse pathologic conditions. Notably, coagulation factors mediate fibrinogenesis and contribute to fibrosis. Thus, we hypothesized that kidney Mo express coagulation factors that contribute to the provisional matrix formation during acute kidney injury (AKI). To test our hypothesis, we probed for Mo-derived coagulation factors after kidney injury and uncovered that both infiltrating and kidney-resident Mo 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 Mo during AKI and CKD. Our in vitro experiments revealed that the upregulation of coagulation factors in Mo occurs in a Ca2 + -dependent manner. Taken together, our study demonstrates that kidney Mo populations express key coagulation factors following local injury, suggesting a novel effector mechanism of Mo contributing to kidney fibrosis.

키워드