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Researchers pinpoint sources of fibrosis-promoting cells that ravage organs
Date:7/1/2013

HOUSTON Scientists have tracked down and quantified the diverse origins of cells that drive fibrosis, the incurable, runaway wound-healing that scars and ultimately destroys organs such as the lungs, liver and kidneys.

Findings from research conducted at Beth Israel Deaconess Medical Center, Harvard Medical School and Massachusetts Institute of Technology in Boston and continued at The University of Texas MD Anderson Cancer Center are reported in an advance online publication at Nature Medicine on June 30.

"Answering a fundamental question about the origin of these cells by identifying four separate pathways involved in their formation allows us to look at ways to block those pathways to treat fibrosis," said senior author Raghu Kalluri, Ph.D., M.D., MD Anderson chair and professor of Cancer Biology. "It's highly unlikely that a single drug will work."

"In addition to being lethal in its own right, fibrosis is a precursor for the development of cancer and plays a role in progression, metastasis and treatment resistance," Kalluri said. "In some cancers, such as pancreatic cancer, up to 95 percent of tumors consist of fibrotic stroma."

Working in genetic mouse models of kidney fibrosis, Kalluri and colleagues identified four sources of cells called myofibroblasts, the dominant producers of collagen. Collagen normally connects damaged tissue and serves as scaffolding for wound-healing. As healing occurs, myofibroblasts and collagen usually diminish or disappear.

In fibrosis, collagen production marches on. While inflammation-inhibiting drugs can sometimes slow its progress, fibrosis now is treatable only by organ transplant.

Myofibroblasts have four types of parents

The researchers employed a fate-mapping strategy to track cells on their way to becoming myofibroblasts. In fate mapping, the promoter of a protein expresses a color inside a cell that remains with the cell no matter wh
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0655
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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