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Related Concept Videos

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Amplifying Signals via Enzymatic Cascade01:22

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After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
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Related Experiment Video

Updated: Mar 26, 2026

Isolation of Papillary and Reticular Fibroblasts from Human Skin by Fluorescence-activated Cell Sorting
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Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21.

Diana Ronai Dunshee1, Travis W Bainbridge2, Noelyn M Kljavin3

  • 1From Molecular Biology.

The Journal of Biological Chemistry
|January 23, 2016
PubMed
Summary

Fibroblast activation protein (FAP) inactivates the hormone FGF21. Inhibiting FAP stabilizes FGF21, offering a potential therapy for metabolic disorders like obesity and type 2 diabetes.

Keywords:
FGFFGF21dipeptidyl peptidase IV (DPPIV)fibroblast activation protein (FAP)metabolic diseaseprotease inhibitorproteolytic enzymeserine protease

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Area of Science:

  • Endocrinology
  • Metabolic disease research
  • Enzymology

Background:

  • Fibroblast activation protein (FAP) is an enzyme implicated in various physiological and pathological processes.
  • Fibroblast Growth Factor 21 (FGF21) is a hormone known for its metabolic benefits, including anti-obesity and insulin-sensitizing effects.
  • The endogenous regulation and degradation pathways of FGF21 are not fully elucidated.

Purpose of the Study:

  • To identify the specific enzyme responsible for the proteolytic cleavage and inactivation of endogenously produced human FGF21.
  • To investigate the potential of targeting this enzyme for therapeutic intervention in metabolic diseases.

Main Methods:

  • Utilized biochemical assays to identify the protease cleaving human FGF21.
  • Employed a selective chemical inhibitor of FAP, FAP immunodepletion, and genetic deletion of Fap to assess its effect on FGF21 stability.
  • Administered a selective FAP inhibitor to cynomolgus monkeys to measure changes in circulating intact FGF21 levels.

Main Results:

  • Identified fibroblast activation protein (FAP) as the primary enzyme that cleaves and inactivates human FGF21.
  • Demonstrated that FAP inhibition (chemical, immunologic, or genetic) stabilizes recombinant human FGF21 in serum.
  • Showed that acute administration of a selective FAP inhibitor increases circulating intact FGF21 levels in non-human primates.

Conclusions:

  • Fibroblast activation protein (FAP) plays a key role in the degradation of FGF21.
  • Selective FAP inhibition represents a promising therapeutic strategy to enhance endogenous FGF21 activity.
  • This approach holds potential for treating metabolic disorders such as obesity, type 2 diabetes, and non-alcoholic steatohepatitis.