title: The role of integrin alpha(v)beta (8) in neonatal hypoxic-ischemic brain injury.
abstract: Integrin alpha(v)beta(8) plays an important role in cerebral vascular development. It has been proven that alpha(v)beta(8) is a key factor for transforming growth factor-beta1 (TGF-beta1) activation in epithelial cells. However, it is not clear whether alpha(v)beta(8) can activate TGF-beta1 and play a role in protection during neonatal hypoxic-ischemic brain injury. In this study, we investigated the relationship between alpha(v)beta(8) and TGF-beta1 activation, and thus the effects of TGF-beta1 activation in the protection of neurons after hypoxia-ischemia (HI). Astrocytes and neurons from rat brains were cultured and then subjected to oxygen-glucose deprivation to generate HI model in vitro. beta(8) expression was determined using immunocytochemistry, western blot, and reverse-transcriptase polymerase chain reaction. TGF-beta1 activation was determined by TGF-beta bioassay in a tested cell (astrocyte) and a reporter cell co-culture system. The pro-apoptotic protein, cleaved caspase-3, and the anti-apoptotic protein, Bcl-2 and Bcl-xL, were detected using western blot. Cellular apoptosis was detected with TUNEL. We found that beta(8) expression was stronger in astrocytes than that in neurons under normoxia. HI resulted in a rapid and persistent increase of beta(8) expression in astrocytes, but only in a slight and transient increase in neurons. Astrocytes beta(8) could induce TGF-beta1 leading to upregulation of Bcl-2 and Bcl-xL, and thus attenuated neuronal apoptosis. The present findings suggest that beta(8) protecting the brain against neonatal HI injury through TGF-beta1 signaling pathway, which may have implications for the treatment of HI brain injury.
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.forename: Xihong
authors.initials: X
authors.lastname: Li
authors.forename: Deyuan
authors.initials: D
authors.lastname: Li
authors.forename: Fengyan
authors.initials: F
authors.lastname: Zhao
authors.forename: Meng
authors.initials: M
authors.lastname: Mao
authors.forename: Donna
authors.initials: D
authors.lastname: Ferriero
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000172:deficiency*; D000860:Hypoxia / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D018709:Statistics, Nonparametric; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494813:Bcl2l1 protein, rat; C088831:MYBL1 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051020:bcl-X Protein; D005947:Glucose; D010100:Oxygen