Objective To investigate the effect of high-fat diet-induced obesity on oxidative stress and klotho promoter methylation in lung tissue of C57/BL6 mice. Methods Mice in the control group were feed with the normal diet,and mice in the obesity group were feed with high-fat diet. The lung tissue level of uperoxide dis-mutase(SOD)and malondialdehyde(MDA)were determined by using mice enzyme-linked immunosorbent assay (ELISA)kit. The klotho mRNA and protein expression was determined by qPCR and Western-blot ,respectively. The Klotho gene methylation status was determined by methylation specific PCR(MS-PCR). Results Compared with the control group,mice in the obesity group had high level of oxidative stress in lung tissue. Meanwhile,mice in the experimental group had lower levels of klotho mRNA and protein expression than those in the control group. The high-fat diet increased the degree of Klotho gene methylation. Conclusion High-fat diet could lead injure in lung tissue in C57/BL6 mice,klorho promoter methylation may play an important role involved in the process.

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
Administration, Oral ; Anilides ; pharmacology ; Animals ; Bone Diseases, Developmental ; chemically induced ; Cell Proliferation ; drug effects ; physiology ; Female ; Frontal Bone ; abnormalities ; Hedgehog Proteins ; antagonists & inhibitors ; Limb Deformities, Congenital ; chemically induced ; Mice ; Micrognathism ; chemically induced ; Osteogenesis ; drug effects ; Pregnancy ; Pyridines ; pharmacology ; Signal Transduction ; drug effects