PPAR gamma agonists: inhibition of fibrosis
Rochester, NY -
The understanding how to modulate the balance between generation of new functional tissue and creation of a fibrotic scar would allow for the treatment of numerous conditions associated with scar tissue deposition.
It is known that stem cells can help to heal scarred tissue ranging from myocardium, to hepatic parenchymal tissue, to lung tissue. There however other studies that show in some injury systems that bone marrow derived cells contribute to the generation of the fibrotic tissue. Accordingly it would be very advantageous if agents where found that could be pharmacologically administered to shift the balance from fibrotic tissue generation to generation of functional tissue. A recent publication (Lakatos et al. The Role of PPARs in Lung Fibrosis. PPAR Res. 2007:71323) reviews the possibility of using agonists of PPAR to inhibit fibrosis.
The paper makes the following interesting points:
Peroxisome proliferator-activated receptors (PPARs) are a form of nuclear receptors that are activated by their ligands to become transcription factors. PPARs are similar to the retinoid, thyroid hormone and receptors for steroids.
Agonists of PPAR, particularly PPAR gamma are clinically used today particularly for the treatment of diabetes.
PPAR agonists are capable of inhibiting fibrosis in animal models of fibrosis such as bleomycin induced fibrosis.
PPAR agonists suppress hepatic stellate cell production of collagen after injury, mesenchymal stem cells also do this
PPAR agonists suppress fibrosis in liver, kidney, and cardiac models.
PPAR alpha knockout mice have higher levels of fibrosis
Agonists of the PPAR beta/delta receptors enhance the positive effects of PPAR gamma agonists in terms of inhibiting fibrosis.
The fibrotic activites of TGF-beta are inhibited by PPAR-gamma agonists.
These important observations may support the use of stem cells together with various clinically approved PPAR-gamma agonists.
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4 Comments | Add Comment
StemCellPatents.com said...
Conceptually, however there are so many different interactions going on that who knows?
Mary said...
Are there any studies going on for humans that anyone would know about??
Matthew Johnston said...
Studies for what? lung fibrosis or liver fibrosis? did you check the www.clinicaltrials.gov site? that is usually a good place to start
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Mary said...
Would the PPAR work in the presence of HCV?