Transforming growth factor-beta1 regulates the fate of cultured spinal cord-derived neural progenitor cells.
OBJECTIVE
We have evaluated the physiological roles of transforming growth factor-beta1 (TGF-beta1) on differentiation, migration, proliferation and anti-apoptosis characteristics of cultured spinal cord-derived neural progenitor cells.


METHODS
We have used neural progenitor cells that had been isolated and cultured from mouse spinal cord tissue, and we also assessed the relevant reaction mechanisms using an activin-like kinase (ALK)-specific inhibitory system including an inhibitory RNA, and found that it involved potential signalling molecules such as phosphatidylinositol-3-OH kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2).


CONCLUSIONS
Transforming growth factor-beta1-mediated cell population growth was activated after treatment and was also effectively blocked by an ALK41517-synthetic inhibitor (4-(5-benzo(1,3) dioxol-5-yl-4-pyridine-2-yl-1H-imidazole-2-yl) benzamide (SB431542) and ALK siRNA, thereby indicating the involvement of SMAD2 in the TGF-beta1-mediated growth and migration of these neural progenitors cells (NPC). In the present study, TGF-beta1 actively induced NPC migration in vitro. Furthermore, TGF-beta1 demonstrated extreme anti-apoptotic behaviour against hydrogen peroxide-mediated apoptotic cell death. At low dosages, TGF-beta1 enhanced (by approximately 76%) cell survival against hydrogen peroxide treatment via inactivation of caspase-3 and -9. TGF-beta1-treated NPCs down-regulated Bax expression and cytochrome c release; in addition, the cells showed up-regulated Bcl-2 and thioredoxin reductase 1. They also had increased p38, Akt and ERK1/2 phosphorylation, showing the involvement of both the PI3K/Akt and MAPK/ERK1/2 pathways in the neuroprotective effects of TGF-beta1. Interestingly, these effects operate on specific subtypes of cells, including neurones, neural progenitor cells and astrocytes in cultured spinal cord tissue-derived cells. Lesion sites of spinal cord-overexpressing TGF-beta1-mediated prevention of cell death, cell growth and migration enhancement activity have been introduced as a possible new basis for therapeutic strategy in treatment of neurodegenerative disorders, including spinal cord injuries.
Park
S M
SM
Department of Physiology, College of Medicine, Pusan National University, Pusan, South Korea.
Jung
J S
JS
Jang
M S
MS
Kang
K S
KS
Kang
S K
SK
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D054481:Thioredoxin Reductase 1 / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C494828:Bax protein, rat; D001549:Benzamides; D004149:Dioxoles; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D054481:Thioredoxin Reductase 1; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases