Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

Area of Science:

• Cell Biology
• Dermatology
• Molecular Biology

Background:

• Fibroblast migration is crucial for skin wound healing.
• Basic fibroblast growth factor (bFGF) promotes fibroblast migration, but its mechanism is unclear.
• The Hedgehog (Hh) signaling pathway's role in wound healing requires further elucidation.

Purpose of the Study:

• To investigate the mechanism by which bFGF regulates fibroblast migration.
• To determine the role of the Hh canonical pathway in bFGF-mediated fibroblast migration and skin wound healing.
• To identify potential therapeutic targets for wound healing.

Main Methods:

• RNA-sequencing (RNA-seq) to identify regulated genes.
• Quantitative real-time PCR (qRT-PCR) for gene expression analysis.
• Western blot and siRNA transfection assays to confirm protein interactions and pathways.
• In vivo studies on skin wound healing models.

Main Results:

• bFGF up-regulates Hh pathway genes, including Smoothened (Smo) and Gli1.
• Activation of the Hh pathway via Smo promotes fibroblast migration, invasion, and skin wound healing.
• Inhibition of Gli1/Gli2 by GANT61 reduces these effects.
• Smo acts upstream of the PI3K-JNK-β-catenin pathway to drive cell migration.
• β-catenin feedback activates Hh signaling, indicating a regulatory loop.

Conclusions:

• A novel mechanism reveals bFGF regulates fibroblast migration through the Hh signaling pathway.
• The Hh pathway, regulated by Smo and β-catenin, is essential for bFGF-induced fibroblast migration and wound healing.
• Targeting the bFGF-Hh signaling axis offers a promising therapeutic strategy for enhancing wound healing.