title: Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats.
abstract: Peripheral neuropathy is common and ultimately accounts for significant morbidity in diabetes. Recently, several neurotrophic factors have been used to prevent progression of diabetic neuropathy. In this study, we gave repeated intramuscular injections of the human hepatocyte growth factor (HGF) gene percutaneously, using liposomes containing the hemagglutinating virus of Japan (HVJ), to examine therapeutic efficacy of nonviral gene transfer of HGF for experimental diabetic sensorimotor neuropathy in rats. Experimental diabetes induced by intraperitoneal injection of streptozotocin resulted in a marked tactile allodynia (but not in a thermal hyperalgesia), in a reduction of both the conduction velocity and the amplitude, and in a decreased laser Doppler flux of the nerve and the muscle at 6 weeks after the induction. All these changes were significantly reversed by repeated gene transfer of HGF. Furthermore, we analyzed the density of endoneurial capillaries and morphometrical changes of the nerve. The density of endoneurial capillaries, disclosing marked reduction in diabetic rats, was also reversed significantly by repeated gene transfer of HGF; however, no considerable differences were observed morphometrically in either myelinated or unmyelinated axons. These results suggest that nonviral HVJ liposome-mediated gene transfer of human HGF has potential for the safe effective treatment of diabetic sensorimotor neuropathy.
authors.affiliation: Department of Orthopaedic Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan 359-8513. grd1505@gr.ndmc.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Kato
authors.forename: Koichi
authors.initials: K
authors.lastname: Nemoto
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Maki
authors.initials: M
authors.lastname: Uenoyama
authors.forename: Tomosumi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Fujikawa
mesh_terms: D000818:Animals; D003929:Diabetic Neuropathies / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015870:Gene Expression / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008081:Liposomes; D008297:Male; D009431:Neural Conduction; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000473:pathology; D029082:Sendai virus
chemical_list: D008081:Liposomes; D017228:Hepatocyte Growth Factor