Inhibition of PDGF signal suppresses the fibrotic scar formation and promotes axonal regeneration in a mouse nigrostriatal lesion model.

Authors

Yukari Komuta, Junko Kimura-Kuroda, Yuko Seko, Yu Hongo, Kazushi Suzuki, Hitoshi Kawano

Published in

American journal of physiology. Cell physiology. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

After traumatic injury to the central nervous system (CNS), meningeal fibroblasts migrate into the lesion site and synthesize extracellular matrix (ECM) molecules, leading to the formation of a fibrotic scar (FS). The FS prevents axonal regeneration by releasing inhibitory ECMs, including chondroitin sulfate proteoglycans, Slits, and semaphorin 3A. Platelet-derived growth factor (PDGF) has been implicated in fibrotic diseases, but its specific contribution to FS formation has remained unclear. In this study, we investigated the role of PDGF signaling in scar formation after CNS injury. In the lesioned mouse brain, PDGFRα and PDGFRβ were strongly expressed within the FS, while PDGF-B was detected in reactive astrocytes surrounding the lesion. Administration of AG1296, a PDGF signaling inhibitor, into the lesion site significantly reduced FS formation and allowed partial regeneration of transected dopaminergic axons. Complementary in vitro studies using rat meningeal fibroblasts demonstrated that PDGF signaling promoted both proliferation and migration of fibroblasts. Moreover, PDGF stimulation enhanced expression of transforming growth factor-β (TGF-β), a cytokine known to drive ECM deposition and scar formation. These findings provide the first direct evidence that inhibition of PDGF signaling suppresses FS formation and facilitates axonal regeneration after CNS lesioning. Our results suggest that PDGF signaling functions during the early phase of FS development by promoting fibroblast proliferation, migration, and TGF-β expression. Thus, targeting PDGF signaling may represent a promising therapeutic strategy for limiting scar formation and improving neural repair following human CNS injury.

PMID:
42809441
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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