title: The HIF-1 inhibitor YC-1 decreases reactive astrocyte formation in a rodent ischemia model.
abstract: Astrocytes become reactive after central nervous system injury, re-expressing glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and nestin. Hypoxia-inducible transcription factor alpha (HIF-1α) is an important transcription factor for several genes including the VEGF and nestin genes, the expression of which generate reactive astrocytes and cause gliosis after cerebral ischemia. To evaluate the role of HIF-1α in reactive astrocyte formation, we applied the potent HIF-1α inhibitor YC-1 to a focal cerebral ischemia model and analyzed the expression of HIF-1α, VEGF, nestin, and GFAP. Quantitative real-time reverse transcription polymerase chain reaction and western blot analyses demonstrated that the expression of HIF-1α and its downstream genes (VEGF and nestin) were markedly attenuated in the YC-1-treated group versus the control group (HIF-1α, VEGF: p < 0.01; nestin: p < 0.05). GFAP expression was also effectively inhibited in the YC-1-treated group (p < 0.05). Immunohistochemical evaluations showed that GFAP-positive (GFAP+) cells in the YC-1-treated group were sparse in the peri-infarct area, while an immunofluorescence assay revealed that the number of VEGF+/GFAP+ and nestin+/GFAP+ reactive astrocytes were decreased in the YC-1-treated group (p < 0.05). These results demonstrate that HIF-1α suppression decreases the formation of reactive astrocytes and gliosis that occur following focal ischemia.
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School Gwangju, Korea ; Department of Pathology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Jong-In
authors.initials: JI
authors.lastname: Na
authors.affiliation: Forensic Medicine Division, National Forensic Service Jangseong-gun, Jeollanam-do, Korea.
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Na
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Choi
authors.affiliation: Department of Pathology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Neurology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Neurology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Kang-Ho
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Neurosurgery, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Jeong-Kil
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ilsan Paik Hospital, Inje University Goyang, Korea.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School Gwangju, Korea ; Department of Pathology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Jong-Tae
authors.initials: JT
authors.lastname: Park
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School Gwangju, Korea ; Department of Pathology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Kim
keywords: Astrogliosis; GFAP; HIF-1α; VEGF; YC-1; nestin; reactive astrocyte