title: Hepatocyte growth factor reduces astrocytic scar formation and promotes axonal growth beyond glial scars after spinal cord injury.
abstract: The formation of glial scars impedes growth of regenerating axons after CNS injuries such as spinal cord injury (SCI). Hepatocyte growth factor (HGF), originally identified as a mitogen for hepatocytes, exerts pleiotropic functions in the nervous system. HGF has been implicated in peripheral wound healing via regulation of the transforming growth factor beta (TGFβ), which is also a potent inducer of glial scar formation in CNS. In the present study, we found that HGF completely blocked secretion of TGFβ1 and β2 from activated astrocytes in culture. HGF also prevented expression of specific chondroitin sulfate proteoglycan (CSPG) species. To determine whether HGF inhibits glial scar formation in an in vivo SCI model, HGF overexpressing mesenchymal stem cells (HGF-MSCs) were transplanted into hemisection spinal cord lesions at C4. Transplantation of HGF-MSCs markedly diminished TGFβ isoform levels and reduced the extent of astrocytic activation. In addition, HGF-MSCs also significantly decreased neurocan expression and glycosaminoglycan chain deposition around hemisection lesions. Furthermore, animals treated with HGF-MSCs showed increased axonal growth beyond glial scars and improvement in recovery of forepaw function. Our results indicate that anti-glial scar effects of HGF, together with its known neurotrophic functions, could be utilized to ameliorate functional deficits following SCI.
authors.affiliation: Brain Disease Research Center, Institute for Medical Sciences, and Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Soo Ryeong
authors.initials: SR
authors.lastname: Jeong
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Hwan Goo
authors.initials: HG
authors.lastname: Lee
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Joe
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Haeyoung
authors.initials: H
authors.lastname: Suh-Kim
authors.forename: Byung G
authors.initials: BG
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects*; D001369:Axons / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D002921:Cicatrix / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018737:Hand Strength / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D006801:Humans; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor