Work

Glial Scar-Targeted Modification of Hepatocyte Growth Factor-Derived Peptide for Spinal Cord Injury Therapeutic Repair

Year: 2026

Type: article

Abstract: Spinal cord injury (SCI) causes irreversible neural damage and functional impairment. H-RN is a short peptide originating from the kringle 1 domain of hepatocyte growth factor. Despite its efficacy in inhibiting inflammatory responses, the precise neuroprotective mechanisms of the peptide H-RN in SCI remain unclear. The short peptide CAQK can target the lesion epicenter of SCI. To explore the role of the peptide H-RN in SCI and address the numerous challenges faced by conventional drug therapies, this study developed a synthetic peptide, CAQK-H-RN. Our results revealed that CAQK-H-RN could cross the blood-spinal cord barrier, precisely target the SCI region, and increase drug accumulation at the injury site, thereby reducing glial scar formation, decreasing motor neuron death, and enhancing functional recovery after SCI. RNA sequencing was performed to explore the molecular mechanisms of CAQK-H-RN in SCI, which revealed that CAQK-H-RN inhibited pyroptosis and ameliorated lysosomal membrane permeabilization (LMP)-induced autophagic flux disorders in neurons after SCI. Additionally, CAQK-H-RN alleviated LMP by suppressing acid sphingomyelinase activity through the p38 mitogen-activated protein kinase/Ets-like protein-1 (Elk-1)/early growth response protein 1 (Egr-1) signaling cascade and subsequently enhanced autophagy, thereby mitigating neuronal death. This intravenous therapeutic system centered on the synthetic peptide CAQK-H-RN contributes to the functional restoration of SCI, which may be clinically applicable to spinal cord repair.

Source: Biomaterials Research

DOI: 10.34133/bmr.0431