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.

Frontiers in Medicine
|July 10, 2023
PubMed

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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