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Platelet Polyphosphate Signals Through NFκB to Induce Myofibroblast Differentiation
Patrick M Suess1, Chanel C La2,3, Sreeparna Vappala2,4
1Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Biomolecules
|October 29, 2025
Summary
Platelets release inorganic polyphosphate, which promotes wound healing by transforming fibroblasts into myofibroblasts via RAGE and NFκB signaling. Inhibiting this pathway could treat fibrosis.
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Myofibroblasts are crucial for wound healing and fibrosis.
- Platelets secrete factors that influence wound healing.
- Inorganic polyphosphate (polyP) from platelets attracts fibroblasts and induces a myofibroblast phenotype.
Purpose of the Study:
- To investigate the signaling pathway by which platelet polyphosphate induces myofibroblast differentiation.
- To identify key cell-surface receptors and intracellular molecules involved in this process.
Main Methods:
- Utilized NIH-3T3 cells and primary human fibroblasts.
- Examined the effects of inhibitors targeting cell-surface receptors and intracellular signaling pathways.
- Assessed the role of the receptor for advanced glycation end products (RAGE) and nuclear factor kappa B (NFκB).
- Tested platelet releasates with and without polyP inhibition.
Main Results:
- Polyphosphate-induced myofibroblast differentiation is mediated by RAGE and NFκB.
- Inhibiting RAGE or NFκB blocked the effects of polyphosphate on fibroblasts.
- Platelet releasates induced NFκB signaling and myofibroblast differentiation.
- Blocking polyphosphate in platelet releasates prevented myofibroblast differentiation.
Conclusions:
- Platelet-derived polyphosphate promotes wound healing via RAGE and NFκB signaling, leading to myofibroblast differentiation.
- This pathway presents potential therapeutic targets for enhancing wound healing or managing fibrotic diseases.
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