It is recognized that expression of
AQP4 protein is much greater in
gliomas than in normal tissue. The relationship between AQP4 and
glioma-associated
brain edema is affected by osmotic pressure and
hypoxia. In this study, we detected changes of AQP4 expression in
tumor and peritumoral edematous tissues to analyze the relationship between
AQP4 protein and the
edema index (EI). We also detected expression of
vascular endothelial growth factor (
VEGF) and
hypoxia-inducible factor-1α (HIF-1α) to investigate their relationship with
AQP4 protein, and thus to uncover the molecular
biological mechanisms of AQP4 expression in
glioma-associated
brain edema. Sixty-five patients with brain
glioma were divided into
tumor and peritumor groups. Fresh
tumor specimens, including six cases of grade I
glioma, 18 of grade II, 11 of grade III and 30 of grade IV, and peritumoral edematous tissue specimens (1 cm distant from the
tumor) were resected from these patients, and
AQP4 protein expression levels were detected by western blot. Different AQP4 expression in the
tumor and peritumor groups were compared. The relationship between AQP4 expression levels and the degree of peritumoral
edema, and expression differences in different grades, were analyzed. Immunofluorescence cytochemistry was used to detect positive expression of
AQP4 protein,
VEGF protein, and HIF-1α
protein in
tumor tissue, and differences between expression were analyzed. Western blot showed that AQP4 expression in the peritumor (0.7697 ± 0.0941) and
tumor (0.6934 ± 0.0625) groups was higher than in the control group (0.6215 ± 0.0884), and was highest in the peritumor group (both P < 0.01). AQP4 expression level in the peritumor group was positively correlated with EI (r = 0.677, P < 0.001) whereas AQP4 expression level in the
tumor group was not correlated with EI (r = 0.096, P > 0.05). AQP4 expression increased with higher
tumor grades in the peritumor group, but differences were not significant in the
tumor group. Immunofluorescence cytochemical staining revealed that
AQP4 protein in normal brain tissue was mainly expressed in the cell membrane surface, and that cytoplasm and nuclear staining was shallow. In
glioma cells, AQP4 was widely distributed in the cytoplasm, particularly in the edematous area around the
tumor.
AQP4 protein expression in the
tumor was significantly positively correlated with both
VEGF protein (r = 0.877, P < 0.001) and HIF-1α
protein (r = 0.876, P < 0.001). AQP4 expression was higher in
brain tumor, especially peritumor. The degree of peritumoral
edema correlates with
AQP4 protein expression only in peritumor, whereas AQP4 expression is in accordance with expression of
VEGF and HIF-1α. In
glioma-associated
brain edema, AQP4 is coregulated by osmotic pressure and
hypoxia, with predominance of osmotic regulation, and is redistributed in
glioma cells, mainly in the cytoplasm, and its expression level increased with higher
glioma grades.