title: Role of GATA-6 and Bone Morphogenetic Protein-2 in Dexamethasone-Induced Cleft Palate Formation in Institute of Cancer Research Mice.
abstract: The mechanism of cleft palate induction by dexamethasone is not fully known. Bone morphogenetic protein-2 (BMP-2) has been associated with dexamethasone-induced osteoporosis. In this study, the authors induced cleft palate models in Institute of Cancer Research mice by dexamethasone to investigate the role of BMP-2 and its transcriptional element GATA-6. The authors injected different doses of dexamethasone into pregnant mice (E13), and assessed the histology of the palatal shelf and the expression levels of BMP-2, GATA-6, and specific apoptosis-related proteins. The results showed that cleft palate formation was dependent on dexamethasone dosage, with high incidence (50.55%) at high concentration (50 mg/kg) compared with the low doses (6 mg/kg, 38.10%). Transmission electron microscopy revealed significant cellular changes of the cleft palate shelf, including loose cell connection, cellular swelling, as well as reduced extracellular matrix and mitochondria. Following exposure to dexamethasone, the apoptotic rate in the palate increased with elevated dosage. Western blotting analysis indicated that the expression levels of GATA-6 and BMP-2 were reduced, while the levels of apoptotic proteins bax and caspase-3 were increased. The results of authors' study suggested that dexamethasone-induced cleft palate formation involved apoptosis occurred in a dose-dependent manner. BMP-2 and GATA-6 mediated dexamethasone-induced cleft palate formation.
authors.affiliation: *Department of Hematology and Oncology, First Hospital of Jilin University †College of Chemistry Northeast Normal University ‡Department of Plastic and Aesthetic Surgery, First Hospital of Jilin University §National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Lan
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Yang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.forename: Tian-Ye
authors.initials: TY
authors.lastname: Yang
authors.forename: Chen-Hui
authors.initials: CH
authors.lastname: Xiang
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Rong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D002972:Cleft Palate / Q000139:chemically induced* / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D050993:GATA6 Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D050993:GATA6 Transcription Factor; D003907:Dexamethasone