Coagulation protein tPA wears new hat

In a new study in rodents, Youhua Liu and colleagues at the University of Pittsburgh School of Medicine have identified a new role for the blood clotting protein tPA in the development of renal fibrosis.

Following tPA treatment of rat kidney fibroblasts, collagen was secreted by the cells along with a protein marker of fibroblast activation, alpha-SMA. This protein deposition was independent of the blood clotting effects of tPA, but it did require presence of the protein LRP-1 on the surface of the fibroblasts. These results were confirmed in mice with acute kidney dysfunction. In normal mice, tPA/LRP-1 protein complexes were associated with alpha-SMA in the mouse kidney. However, mice deficient in tPA had reduced levels of both renal proteins. Because tPA is also capable of activating cells outside of the kidneys, the authors concluded from these results that tPA might also be important in the development of lung or liver fibrosis.-Journal of Clinical Investigation