Effects of hypoxia on expression of transforming growth factor-beta1 and its receptors I and II in the amoeboid microglial cells and murine BV-2 cells.
Transforming growth factor-beta1 (TGF-beta1) is widely recognized as a prototype of multifunctional growth factors and master switches in the regulation of key events of development, disease and repair. It is localized in neurons, astrocytes and brain macrophages in altered conditions but its localization in the amoeboid microglial cells (AMC), a nascent brain macrophage in the developing brain has remained unexplored. Here we report expression of TGF-beta1 and its receptors namely, transforming growth factor-beta receptor I (TbetaRI) and transforming growth factor-beta receptor II (TbetaRII) in AMC and BV-2 cells induced by hypoxia. Firstly, increase in TGF-beta1 mRNA expression and TGF-beta1 release was observed in the corpus callosum in postnatal rats subjected to a single hypoxic exposure. RT-PCR and Western blot analysis revealed a concomitant upregulation of TbetaRI and TbetaRII mRNA and protein. Secondly, immunofluorescence labeling showed that the preponderant AMC in the corpus callosum were immunoreactive for TGF-beta1 and its receptors. In rats subjected to hypoxia, immunoexpression of TGF-beta1 and both receptors was markedly enhanced. In longer surviving rats, the AMC transformed into ramified microglia but retained in them the immunoreactivity. In BV-2 cells exposed to hypoxia, TGF-beta1 mRNA expression and release of TGF-beta1 into the medium were significantly increased. It is noteworthy that expression of TbetaRI and TbetaRII mRNA and protein in hypoxic BV-2 cells was reduced indicating a differential response of AMC and BV-2 cells to hypoxia. Notwithstanding, it is unequivocal that AMC in the developing brain express and release TGF-beta1 into the ambient environment. We suggest that this may be a mechanism to help autoregulate microglial activation in adverse conditions via its receptors.
Li
J-J
JJ
Department of Anatomy and Embryology, Faculty of Basic Medical Sciences, Kunming Medical College, 191, West Renmin Road, Kunming, People's Republic of China 650031.
Lu
J
J
Kaur
C
C
Sivakumar
V
V
Wu
C-Y
CY
Ling
E-A
EA