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Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells
04:46

Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells

Published on: March 7, 2025

Role of coagulation factor Xa and protease-activated receptor 2 in human mesangial cell proliferation

Misa Tanaka1, Hidenori Arai, Ning Liu

  • 1Division of Nephrology, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Kidney International
|May 11, 2005
PubMed
Abstract

Insights

Factor Xa promotes mesangial cell proliferation and fibrin deposition via protease-activated receptor 2 (PAR2). A factor Xa inhibitor, DX-9065a, effectively reduced this proliferation and ERK activation, suggesting therapeutic potential.

Area of Science:

  • Nephrology
  • Hematology
  • Cell Biology

Background:

  • Mesangioproliferative glomerulonephritis involves fibrin deposition and mesangial cell proliferation.
  • Coagulation factors like factor Xa are found with fibrin in active IgA nephropathy.

Purpose of the Study:

  • Investigate the role of factor Xa and protease-activated receptor 2 (PAR2) in mesangial cell proliferation and fibrin deposition.
  • Evaluate the anti-proliferative effects of the factor Xa inhibitor DX-9065a in human mesangial cells.

Main Methods:

  • Assessed DX-9065a's effect on factor Xa-induced mesangial cell proliferation using thymidine incorporation and cell counts.
  • Measured extracellular regulated kinase (ERK) activation and fibrin production in response to factor Xa and DX-9065a.

Main Results:

  • Factor Xa dose-dependently increased mesangial cell proliferation and ERK activation, both inhibited by DX-9065a.
  • DX-9065a also reduced factor Xa-induced fibrin deposition.
  • Factor Xa-induced proliferation and ERK activation were blocked by PD98059, but not by a PAR1 antagonist.

Conclusions:

  • Factor Xa induces mesangial cell proliferation via ERK activation through PAR2.
  • PAR2 plays a key role in factor Xa-mediated mesangial cell proliferation.
  • DX-9065a shows promise for regulating mesangial cell proliferation and inhibiting mesangial coagulation.

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