JCI table of contents: Nov. 21, 2007(ccumulation in the kidney is responsible...),Health

Date:11/21/2007

ccumulation in the kidney is responsible for fibrosis, including the deposition of the protein collagen by specialized cells named fibroblasts. 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.

TITLE: Tissue-type plasminogen activator promotes murine myofibroblast activation through LDL receptorrelated protein 1mediated integrin signaling

AUTHOR CONTACT:

Youhua Liu
University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Phone: (412) 648-8253; Fax: (412) 648-1916; E-mail: liuy@upmc.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=32301

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ONCOLOGY: The estrogen receptor enables a pre-cancerous mutation to reach its potential

Most cases of primary breast cancer are characterized by aberrant expression of the protein c-Rel. A causal role for c-Rel in the development of breast cancer has been shown in mice. However, the tumors take a long time to develop and it has been
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Contact: Karen Honey press_releases@the-jci.org 215-573-1850 Journal of Clinical Investigation Source:Eurekalert

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