RESUMO
The role of Ahnak in obesity has been reported previously. Loss of Ahnak leads to decreased Bmp4/Smad1 signaling, resulting in the downregulation of adipocyte differentiation. However, the biological significance of Ahnak remains largely unknown. In this study, we demonstrate that Ahnak-mediated impaired adipogenesis results in decreased Bmpr1α transcriptional expression. To confirm this, Ahnak siRNA was used to knock-down Ahnak in C3H10T1/2 and primary stromal vascular fraction cells. Ahnak siRNA transfected cells showed suppression of Bmpr1α expression and decreased BMP4/ Bmpr1α signaling. The differential adipogenesis was further confirmed by knock-down of Bmpr1α in C3H10T1/2 cells, which resulted in reduced adipogenesis. Moreover, stable Ahnak knock-out C3H10T1/2 cells stably transfected with Ahnak CRISPR/Cas9 plasmid suppressed expression of Bmpr1α and prevented differentiation into adipocytes. Furthermore, we developed immortalized pre-adipocytes from wild-type or Ahnak Knock-out mice's stromal vascular fraction (SVF) to confirm the function of Ahnak in pre-adipocyte transition. Immortalized Ahnak knock-out SVF cells showed lower level of Bmpr1α expression, evidence by their impaired BMP4/Bmpr1α signaling. Upon adipogenic induction, immortalized Ahnak knock-out SVF cells exhibited a marked decrease in adipocyte differentiation compared with immortalized wild-type pre-adipocytes. Furthermore, over-expression of Bmpr1α restored the adipogenic activity of Ahnak knock-out C3H10T1/2 cells and immortalized Ahnak knock-out SVF cells. Our data reveal the missing link in Ahnak-mediated adipose tissue remodeling and suggest that precise regulation of Ahnak in adipose tissue might have a therapeutic advantage for metabolic disease treatment.
Assuntos
Adipócitos/fisiologia , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Transcrição Gênica/genética , Adipogenia/genética , Tecido Adiposo/fisiologia , Animais , Diferenciação Celular/genética , Linhagem Celular , Regulação para Baixo/genética , Regulação da Expressão Gênica/genética , Masculino , Camundongos , Camundongos Knockout , Obesidade/genéticaRESUMO
X-ray photoelectron spectroscopy spectra and transmission electron microscopy images showed that SnO2 nanoparticles were randomly distributed in the polystyrene (PS) layer. Capacitance-voltage (C-V) measurements on the Al/SnO, nanoparticles embedded in PS layer/p-Si devices at 300 K showed a clockwise hysteresis with a large flatband voltage shift due to the existence of SnO2 nanoparticles. Capacitance-time measurements showed that the devices exhibited excellent memory retention characteristics at ambient conditions. The writing and the erasing mechanisms for the Al/SnO, nanoparticles embedded in PS layer/p-Si devices are described on the basis of the C-V results and energy band diagrams.
