“…Our results reveal ependymal cells as novel targets for VEGF and TGF- . Ependymal microvilli are central to maintaining homeostasis and the transport of cerebrospinal fl uid (CSF) through the ventricles ( 51 ); furthermore, enzymes localized to the microvilli mediate signaling and transport of molecules between the CSF and ependyma ( 52 ). Ependymal cells express TGF- R2 during development ( 53 ), but the action of TGF- on these cells in the adult has not been reported.…”
Section: Neutralization Of Vegf and Tgf- Results In Cortical Periventricular Focal Lesionsmentioning
Although the role of vascular endothelial growth factor (VEGF) in developmental and pathological angiogenesis is well established, its function in the adult is less clear. Similarly, although transforming growth factor (TGF) β is involved in angiogenesis, presumably by mediating capillary (endothelial cell [EC]) stability, its involvement in quiescent vasculature is virtually uninvestigated. Given the neurological findings in patients treated with VEGF-neutralizing therapy (bevacizumab) and in patients with severe preeclampsia, which is mediated by soluble VEGF receptor 1/soluble Fms-like tyrosine kinase receptor 1 and soluble endoglin, a TGF-β signaling inhibitor, we investigated the roles of VEGF and TGF-β in choroid plexus (CP) integrity and function in adult mice. Receptors for VEGF and TGF-β were detected in adult CP, as well as on ependymal cells. Inhibition of VEGF led to decreased CP vascular perfusion, which was associated with fibrin deposition. Simultaneous blockade of VEGF and TGF-β resulted in the loss of fenestrae on CP vasculature and thickening of the otherwise attenuated capillary endothelium, as well as the disappearance of ependymal cell microvilli and the development of periventricular edema. These results provide compelling evidence that both VEGF and TGF-β are involved in the regulation of EC stability, ependymal cell function, and periventricular permeability.
“…Our results reveal ependymal cells as novel targets for VEGF and TGF- . Ependymal microvilli are central to maintaining homeostasis and the transport of cerebrospinal fl uid (CSF) through the ventricles ( 51 ); furthermore, enzymes localized to the microvilli mediate signaling and transport of molecules between the CSF and ependyma ( 52 ). Ependymal cells express TGF- R2 during development ( 53 ), but the action of TGF- on these cells in the adult has not been reported.…”
Section: Neutralization Of Vegf and Tgf- Results In Cortical Periventricular Focal Lesionsmentioning
Although the role of vascular endothelial growth factor (VEGF) in developmental and pathological angiogenesis is well established, its function in the adult is less clear. Similarly, although transforming growth factor (TGF) β is involved in angiogenesis, presumably by mediating capillary (endothelial cell [EC]) stability, its involvement in quiescent vasculature is virtually uninvestigated. Given the neurological findings in patients treated with VEGF-neutralizing therapy (bevacizumab) and in patients with severe preeclampsia, which is mediated by soluble VEGF receptor 1/soluble Fms-like tyrosine kinase receptor 1 and soluble endoglin, a TGF-β signaling inhibitor, we investigated the roles of VEGF and TGF-β in choroid plexus (CP) integrity and function in adult mice. Receptors for VEGF and TGF-β were detected in adult CP, as well as on ependymal cells. Inhibition of VEGF led to decreased CP vascular perfusion, which was associated with fibrin deposition. Simultaneous blockade of VEGF and TGF-β resulted in the loss of fenestrae on CP vasculature and thickening of the otherwise attenuated capillary endothelium, as well as the disappearance of ependymal cell microvilli and the development of periventricular edema. These results provide compelling evidence that both VEGF and TGF-β are involved in the regulation of EC stability, ependymal cell function, and periventricular permeability.
“…As the indicator enzyme, AKP indicates the absorptive capacity of the intestine (Cuvier‐Péres & Kestemont, ). Na + /K + ‐ATPase and γ‐GT play important roles in the active transport of amino acids and absorption of most amino acids in the intestine (Geering, ; Ogawa, Shiozawa, Hiraoka, Takeuchi, & Aiso, ). In this study, the activities of AKP, Na + /K + ‐ATPase, and γ‐GT initially increased with supplementation levels up to 3% but decreased with further increase in supplementation levels.…”
This study aimed to assess the effects of replacing fish meal with cottonseed meal protein hydrolysate (CPH) on the growth, intestinal function, growth hormone/insulin-like growth factor I (GH/IGF-I) axis, and inflammation of blunt snout bream, Megalobrama amblycephala. A total of 300 fish (38.66 ± 0.08 g) were allocated into five groups and fed either the basal diet (CPH 0) or the basal diet that replaced fish meal with 1% (CPH 1), 3% (CPH 3), 5% (CPH 5), and 7% CPH (CPH 7). Dietary CPH 3 increased the activities of protease, Na + /K +-ATPase, amylase, creatine kinase, and γ-glutamyl transpeptidase; microvillus length in the anterior and mid intestines; and the mRNA levels of GH, growth hormone receptor (GHR), and IGF-I without any negative effects on growth. Dietary CPH 7 increased the mRNA levels of tumor necrosis factor-α, interleukin-6, IκB kinase alpha, and nuclear factor κB but decreased the transcript level of inhibitor of κB-α (p < .05). Therefore, replacing fish meal with CPH 3 improved intestinal function and the transcription of GH/IGF-I axis genes without
“…It can be hydrolyzed to its γ-glutamyl moiety and cysteinylglycine, the latter of which can be further broken down in times of cellular stress so that the released amino acids can be taken up by corresponding transporters and reused by cells [45]. The capacity to cleave this γ-glutamyl bond is a unique function of the enzyme γ-glutamyl transferase (GGT), a ubiquitous enzyme located at an exo-facial position in the cellular plasma membrane primarily in tissues having secretory or absorptive functions, including the choroid plexus [46], [47] as well as cerebral microvessels, where it plays an integral role in maintaining blood brain barrier integrity [48].…”
BackgroundUnderstanding the early relationship between brain tumor cells and their environment could lead to more sensitive biomarkers and new therapeutic strategies. We have been using a rodent model of neurocarcinogenesis in which all animals develop brain tumors by six months of age to establish two early landmarks in glioma development: the appearance of a nestin+ cell at thirty days of age and the appearance of cellular hyperplasia between 60 and 120 days of age. We now report an assessment of the CSF proteome to determine the changes in protein composition that occur during this period.Materials and MethodsNestin+ cell clusters and microtumors were assessed in 63 ethylnitrosourea-exposed rats on 30, 60, and 90 days of age. CSF was obtained from the cisterna magna from 101 exposed and control rats at 30, 60, and 90 days and then analyzed using mass spectrometry. Differentially expressed peaks were isolated and identified.ResultsNestin+ cells were noted in all ethylnitrosourea-exposed rats assessed pathologically. Small microtumors were noted in 0%, 18%, and 67% of 30-, 60-, and 90-day old rats, respectively (p<0.05, Chi square). False Discovery Rate analysis of peak intensities showed that the number of true discoveries with p<0.05 increased markedly with increasing age. Isolation and identification of highly differentially detected proteins at 90 days of age revealed increases in albumin and a fragment of α1 macroglobulin and alterations in glutathionylated transthyretin.ConclusionsThe presence of increased albumin, fragments of cerebrospinal fluid proteins, and glutathione breakdown in temporal association with the development of cellular hyperplasia, suggests that, similar to many other systemic cancers, inflammation and oxidative stress is playing an important early role in the host’s response to brain tumor development and may be involved in affecting the early growth of brain tumor.
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