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Preparation, Purification, and Use of Fatty Acid-containing Liposomes
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A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors: GPR40 and GPR84

Lyne Gagnon1, Martin Leduc1, Jean-Francois Thibodeau2

  • 1Prometic BioSciences Inc., Laval, Québec, Canada.

The American Journal of Pathology
|February 19, 2018
PubMed

Insights

GPR40 and GPR84 receptors are involved in organ fibrosis. The drug PBI-4050 targets these receptors, showing significant antifibrotic effects across multiple organs, suggesting potential for treating fibrosis-related diseases.

Area of Science:

  • Molecular biology
  • Pharmacology
  • Pathophysiology

Background:

  • Organ fibrosis is a significant clinical challenge requiring novel therapeutic strategies.
  • G protein-coupled receptors GPR40 and GPR84, linked to metabolic and inflammatory conditions, have not been previously associated with fibrosis.
  • Understanding the role of GPR40 and GPR84 in fibrotic diseases is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of GPR40 and GPR84 in organ fibrosis.
  • To evaluate the antifibrotic potential of PBI-4050, a compound targeting GPR40 and GPR84.

Main Methods:

  • Utilized Gpr40- and Gpr84-knockout mouse models to study kidney fibrosis.
  • Employed various kidney injury models: unilateral ureteral obstruction, chronic ischemic injury, and adenine-induced chronic kidney disease.
  • Assessed the antifibrotic effects of PBI-4050 in multiple organ fibrosis models (kidney, liver, heart, lung, pancreas, skin).

Main Results:

  • GPR40 demonstrated a protective role, while GPR84 exhibited a deleterious effect in kidney fibrosis models.
  • PBI-4050 significantly attenuated fibrosis across kidney, liver, heart, lung, pancreas, and skin fibrosis models.
  • The drug's efficacy was linked to its interaction with both GPR40 and GPR84.

Conclusions:

  • GPR40 and GPR84 are identified as key players in fibrosis pathways, with opposing roles.
  • PBI-4050 exhibits broad-spectrum antifibrotic activity, highlighting its therapeutic potential.
  • GPR40 and GPR84 represent promising molecular targets for managing inflammatory and fibrosis-related diseases.

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