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

at happens to it until it dies, Kalluri said.

This was particularly important because two of the four sources of myofibroblasts start out as another cell type and differentiate into the collagen-producing cells.

Their experiments showed:

  • Half of all myofibroblasts are produced by the proliferation of pre-existing resting fibroblasts.
  • Another 35 percent are produced by mesenchymal stem cells that originate in the bone marrow, migrate to the "wound" site, and then differentiate into myofibroblasts.
  • An additional 10 percent are the products of endothelial to mesenchymal transition (EndMT), in which blood vessel cells change into mesenchymal cells, then become myofibroblasts.
  • The final 5 percent come from epithelial to mesenchymal transition (EMT), in which functional cells of an organ sometimes behave like mesenchymal cells and myofibroblasts.

"These differentiation pathways provide leads for drug targets," Kalluri said.

"Combining an antiproliferation drug with therapies that block one or more differentiation pathways could provide a double hit to control fibrosis. We hope to synergize these pathways for the most effective therapeutic response."

Recruitment from the bone marrow, EMT and EndMT appear to rely on transforming growth factor beta 1 (TGF-B1) to differentiate into myofibroblasts.

Pericytes are not involved

Some earlier descriptive studies implicated pericytes connective, contractile cells that surround blood vessels in the creation of myofibroblasts. The researchers tested pericytes via fate-mapping and found that they're not involved in myofibroblast generation.

Deleting pericytes did not improve kidney fibrosis or change the recruitment of myofibroblasts.

While their research focused on kidney fibrosis, the scientists believe their findings will be applicable to other types of fibrosis.

"Recruitment of fibroblasts
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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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