Laboratory Investigation

Kidney International (1997) 51, 687–693; doi:10.1038/ki.1997.99

Thrombomodulin is synthesized by human mesangial cells

Andre Pruna, Nicole Peyri, Madeleine Berard and Marie-Claire Boffa

Service de Néphrologie, Hôpital Foch, Suresnes, and INSERM Unité 353, Hôpital Saint-Louis, Paris, France

Correspondence: Dr Mane-Claire Boffa, INSERM Unité 353, Hôpital Saint-Louis, 1, avenue Claude Vellefaux, 75010 Paris, France.

Received 12 July 1996; Revised 9 September 1996; Accepted 9 September 1996.

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Abstract

Thrombomodulin is synthesized by mesangial cells. Thrombomodulin (TM), an endothelial receptor for thrombin, endowed with a powerful anticoagulant activity, plays an important role in the antithrombogenicity of the vascular endothelium. Its presence within the human renal glomerulus is already known but was thought to be only endothelial. We looked for TM expression in human mesangial cells (MC), both in situ, in freshly prepared glomeruli, and in primary culture. Both fresh and cultured MC were strongly reactive for TM by immunocytochemical methods. Total TM antigen measured on MC lysates and surface TM activity on MC were 0.292 plusminus 0.075 ng/mg of cellular proteins and 1.20 plusminus 0.02 pmole of activated protein C/min/mg of cellular proteins, respectively. As shown by the presence of numerous transcripts detected by in situ hybridization, TM was shown to be synthesized by MC in vivo and in culture. The synthesis of active TM by both endothelial and mesangial cells within the renal glomerulus stresses the importance of its role in maintaining renal hemostatic equilibrium, and sheds some light on the conflicting reports of TM over- and underexpression in glomerulopathies to open a new field for investigation.

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