Efficacy of nonviral gene transfer of human hepatocyte growth factor (HGF) against ischemic-reperfusion nerve injury in rats.
Animals
Disease Models, Animal
Ganglia, Spinal
/ metabolism
Gene Transfer Techniques
Genetic Therapy
/ methods
Genetic Vectors
Hepatocyte Growth Factor
/ genetics
Humans
Hyperalgesia
/ metabolism
Liposomes
/ metabolism
Male
Neuralgia
/ therapy
Rats
Rats, Wistar
Reperfusion Injury
/ therapy
Sciatic Nerve
/ metabolism
Sendai virus
/ genetics
Treatment Outcome
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
04
2020
accepted:
21
07
2020
entrez:
12
8
2020
pubmed:
12
8
2020
medline:
21
10
2020
Statut:
epublish
Résumé
Ischemic neuropathy is common in subjects with critical limb ischemia, frequently causing chronic neuropathic pain. However, neuropathic pain caused by ischemia is hard to control despite the restoration of an adequate blood flow. Here, we used a rat model of ischemic-reperfusion nerve injury (IRI) to investigate possible effects of hepatocyte growth factor (HGF) against ischemic neuropathy. Hemagglutinating virus of Japan (HVJ) liposomes containing plasmids encoded with HGF was delivered into the peripheral nervous system by retrograde axonal transport following its repeated injections into the tibialis anterior muscle in the right hindlimb. First HGF gene transfer was done immediately after IRI, and repeated at 1, 2 and 3 weeks later. Rats with IRI exhibited pronounced mechanical allodynia and thermal hyperalgesia, decreased blood flow and skin temperature, and lowered thresholds of plantar stimuli in the hind paw. These were all significantly improved by HGF gene transfer, as also were sciatic nerve conduction velocity and muscle action potential amplitudes. Histologically, HGF gene transfer resulted in a significant increase of endoneurial microvessels in sciatic and tibial nerves and promoted nerve regeneration which were confirmed by morphometric analysis. Neovascularization was observed in the contralateral side of peripheral nerves as well. In addition, IRI elevated mRNA levels of P2X3 and P2Y1 receptors, and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in sciatic nerves, dorsal root ganglia and spinal cord, and these elevated levels were inhibited by HGF gene transfer. In conclusion, HGF gene transfer is a potent candidate for treatment of acute ischemic neuropathy caused by reperfusion injury, because of robust angiogenesis and enhanced nerve regeneration.
Identifiants
pubmed: 32780756
doi: 10.1371/journal.pone.0237156
pii: PONE-D-20-09804
pmc: PMC7418984
doi:
Substances chimiques
HGF protein, human
0
Liposomes
0
Hepatocyte Growth Factor
67256-21-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0237156Déclaration de conflit d'intérêts
The authors have declared that no competing interest exists.
Références
Vasc Med. 2004 May;9(3):193-8
pubmed: 15675184
Eur J Neurosci. 2002 May;15(9):1444-50
pubmed: 12028354
Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10465-70
pubmed: 8816824
Pain. 1988 Jan;32(1):77-88
pubmed: 3340425
Curr Gene Ther. 2004 Jun;4(2):199-206
pubmed: 15180586
FEBS Lett. 1987 Nov 30;224(2):311-6
pubmed: 3319692
J Neurochem. 2003 May;85(3):810-5
pubmed: 12694407
Nat Neurosci. 1999 Mar;2(3):213-7
pubmed: 10195212
Am J Pathol. 1984 May;115(2):275-87
pubmed: 6326580
Ann Neurol. 2000 Jan;47(1):71-9
pubmed: 10632103
J Neurosci. 2000 Aug 1;20(15):RC90
pubmed: 10899177
Arch Neurol. 2001 May;58(5):761-8
pubmed: 11346371
Genes Dev. 1997 Dec 15;11(24):3341-50
pubmed: 9407027
J Neurosci. 1998 Oct 15;18(20):8369-81
pubmed: 9763480
Exp Neurol. 1985 Feb;87(2):369-76
pubmed: 3967721
Neurotoxicology. 2010 Dec;31(6):709-14
pubmed: 20650289
ASAIO Trans. 1988 Jul-Sep;34(3):188-93
pubmed: 3196507
Sci Rep. 2018 May 29;8(1):8316
pubmed: 29844434
Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(6):588-610
pubmed: 20551596
Brain Res. 1988 May 24;449(1-2):89-96
pubmed: 2456134
Expert Opin Biol Ther. 2015 Mar;15(3):381-90
pubmed: 25633211
Semin Vasc Surg. 2014 Mar;27(1):16-22
pubmed: 25812755
PLoS One. 2010 Sep 28;5(9):
pubmed: 20927397
J Biochem. 1996 Apr;119(4):591-600
pubmed: 8743556
J Vasc Surg. 2018 Feb;67(2):498-505
pubmed: 28943004
Circ Res. 2015 Apr 24;116(9):1540-50
pubmed: 25908727
J Neurosci Methods. 1994 Jul;53(1):55-63
pubmed: 7990513
J Peripher Nerv Syst. 1997;2(1):60-9
pubmed: 10975737
Anesthesiology. 1995 Jan;82(1):60-3
pubmed: 7832336
FASEB J. 2018 Sep;32(9):5119-5131
pubmed: 29913557
Br J Pharmacol. 1999 Jan;126(2):429-36
pubmed: 10077235
Mol Ther. 2013 Jun;21(6):1279-86
pubmed: 23609019
Diabetes. 2005 Mar;54(3):846-54
pubmed: 15734864
Ann Clin Transl Neurol. 2015 May;2(5):465-78
pubmed: 26000320
Diabet Med. 1991;8 Spec No:S63-6
pubmed: 1825961
J Anat. 1994 Oct;185 ( Pt 2):259-66
pubmed: 7961132
J Vasc Surg. 2017 Mar;65(3):695-704
pubmed: 28073665
J Vasc Surg. 2007 Jan;45 Suppl S:S5-67
pubmed: 17223489
J Pharmacol Exp Ther. 2001 Apr;297(1):352-6
pubmed: 11259562
Muscle Nerve Suppl. 1999;8:S247-59
pubmed: 16921640
Nat Med. 2000 Apr;6(4):405-13
pubmed: 10742147
Biomed Pharmacother. 2018 May;101:682-690
pubmed: 29518615
Anesth Analg. 1997 May;84(5):1071-5
pubmed: 9141933
Exp Neurol. 1986 May;92(2):391-7
pubmed: 2420633
J Clin Pathol. 2016 Jul;69(7):575-9
pubmed: 27072686
Mol Cell Neurosci. 2000 Jan;15(1):79-87
pubmed: 10662507
FASEB J. 2003 Apr;17(6):779-81
pubmed: 12586736
Eur J Vasc Endovasc Surg. 2011 Dec;42 Suppl 2:S4-12
pubmed: 22172472
J Atheroscler Thromb. 2000;7(2):71-6
pubmed: 11426585
Neuron. 1996 Dec;17(6):1157-72
pubmed: 8982163
Science. 2000 Apr 14;288(5464):306-13
pubmed: 10764638
Hypertens Res. 2016 Apr;39(4):183-91
pubmed: 26631852
Phys Med Rehabil Clin N Am. 2001 May;12(2):365-80
pubmed: 11345013
J Biochem. 2016 Aug;160(2):77-85
pubmed: 27318359
Vascul Pharmacol. 2006 Jun;44(6):395-405
pubmed: 16698324
Eur J Vasc Endovasc Surg. 2006 Jul;32(1):60-5
pubmed: 16513377
Biomedicines. 2014 Dec 31;3(1):1-31
pubmed: 28536396
J Peripher Nerv Syst. 2002 Mar;7(1):37-43
pubmed: 11939350
Mol Ther. 2009 Jan;17(1):42-50
pubmed: 18941443
Biochem Biophys Res Commun. 1984 Aug 16;122(3):1450-9
pubmed: 6477569
Diabet Med. 1994 Nov;11(9):872-6
pubmed: 7705025