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Intramuscular Delivery of HGF-expressing Recombinant AAV Improves Muscle Integrity and Alleviates Neurological Symptoms in the Nerve Crush and SOD1-G93A Transgenic Mouse Models

Sang Hwan Lee, Nayeon Lee, Subin Kim, Junghun Lee, Wooshik Choi, Seung Shin Yu, Jin Hong Kim, Sunyoung Kim

Biochem Biophys Res Commun. 2019 Sep 24;517(3):452-457.

PMID: 31376938

Abstract:

Hepatocyte growth factor (HGF) is a versatile neurotrophic factor that mediates a variety of cellular activities. In this study, we investigated the effects of intramuscularly injected recombinant AAV vectors expressing HGF in two pathologic conditions: the sciatic nerve crush and the SOD1-G93A transgenic mouse models. AAV serotype 6 (rAAV6) was chosen based on its expression levels in, and capability of moving to, the spinal cord from the injected muscle area. In the nerve crush model, rAAV6-HGF was shown to reduce the degree of mechanical allodynia, increase the cross-sectional area of muscle fibers, promote regrowth of peripheral axons, and improve motor functions. In the SOD1-G93A TG mouse model, rAAV6-HGF increased the mass of the tibialis anterior and gastrocnemius, alleviated disease symptoms, and prolonged survival. Improvements in integrity and functions of muscle in these models seemed to have come from the ability of HGF produced from rAAV6-HGF to regulate the expression of various atrogenes through the control of the FOXO signaling pathway. Our findings suggested that intramuscular injection of rAAV6-HGF might be used to relieve various symptoms associated with muscle atrophy and/or nerve damages observed in a majority of neuromuscular diseases.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42413297 HGF mouse HGF mouse Price
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