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RYK is a GPNMB receptor that drives MASH - PubMed

4 days ago
  • #MASH
  • #therapeutic target
  • #GPNMB-RYK axis
  • RYK is identified as a receptor for GPNMB, driving metabolic-dysfunction-associated steatohepatitis (MASH).
  • GPNMB's secreted ectodomain (G-ECD), not full-length GPNMB, promotes MASH progression.
  • Serum G-ECD levels correlate with MASH severity in human patients.
  • RYK ablation in hepatocytes protects mice from MASH by blocking G-ECD effects.
  • G-ECD binding to RYK activates ERK1/2 signaling, leading to PPARγ-CD36 and SREBP1C pathway activation.
  • Therapeutic strategies targeting the GPNMB-RYK axis show promise in preventing and treating MASH.