Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

Chiba, Yoichi; Murakami, Ryuta; Matsumoto, Koichí; Wakamatsu, Keiji; Nonaka, Wakako; Uemura, Naoya; Yanase, Ken; Kamada, Masaki; Ueno, Masaki

doi:10.3390/ijms21197230

Cited by 23 publications

(33 citation statements)

References 176 publications

(457 reference statements)

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“…Myung et al 3 reported that the choroid plexus is an important circadian clock component, suggesting a great role of the choroid plexus in adjusting circadian rhythm. In addition, it has become well-known that numerous transporters are localized in epithelial cells of the choroid plexus, [36][37][38] indicating more transportation functions of choroid plexus epithelial cells than previously considered those. From these findings, it is likely that choroid plexus dysfunction has significant effects on various brain functions, including cognitive function.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of osteopontin and collagens in choroid plexus of human brains

et al. 2021

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Evidence showing the functional significance of the choroid plexus is accumulating. Although it is clinically wellknown that calcification is frequently seen in the choroid plexus of aged human brains, it is unclear why calcification occurs in the aged choroid plexus and what exert effects on the calcification has. In this study, immunohistochemical localizations of collagens and other molecules related to fibrosis or calcification were investigated on the choroid plexus of autopsied human brains. Densely fibrous or calcified materials were located in the stroma just below the epithelial cells of the choroid plexus of all human brains examined. Immunoreactivity for collagen type I was identified in the stroma just below the epithelial cells, consistent with the densely fibrous or calcified area, whereas that for collagen type III was observed in almost all stroma other than the densely fibrous or calcified areas. Linear or membranous immunoreactivity for collagen type IV was intermittently localized on the epithelium-facing side of the materials, suggesting an injured basement membrane. In addition, clear immunoreactivity for osteopontin was localized on the epithelium-facing side of the fibrous or calcified materials as well as in the cytoplasm of epithelial cells. These findings indicate that collagen type I exists in contact with osteopontin in and around the densely fibrous or calcified materials in the choroid plexus. They suggest that the densely fibrous or calcified materials are deposited in the subepithelial stroma just below an injured basement membrane of epithelial cells via the collagen type I and osteopontin.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of osteopontin and collagens in choroid plexus of human brains

et al. 2021

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“…Of interest, an isoform of the Na + -coupled glucose transporter (SGLT2; SLC5A2), which was previously annotated to sole expression in the proximal tubules [78], was here detected in the choroidal transcriptome, albeit at a lower relative expression level (6 TPM) than that observed in the proximal tubule sample (22 TPM). The choroidal transcript abundance of SGLT2 is confirmatory of its recently demonstrated protein expression in mouse and human choroid plexus [79, 80]. The proposed selective SGLT2 expression in the proximal tubules led to development of SGLT2 inhibitors as a selective treatment option for type 2 diabetes mellitus [81, 82].…”

Section: Discussionmentioning

confidence: 87%

“…The proposed selective SGLT2 expression in the proximal tubules led to development of SGLT2 inhibitors as a selective treatment option for type 2 diabetes mellitus [81, 82]. Such approach may have to be reconsidered based on SGLT2 expression in choroid plexus (this study and [79, 80]), where the transport protein could potentially partake in CSF secretion, like its homologue, SGLT1, participates in fluid transport across the small intestine [83].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus

Andreassen¹,

Toft-Bertelsen²,

Wardman³

et al. 2022

Preprint

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Background: Dysregulation of brain fluid homeostasis associates with brain pathologies in which fluid accumulation leads to elevated intracranial pressure. Surgical intervention remains standard care, since specific and efficient pharmacological treatment options are limited for pathologies with disturbed brain fluid homeostasis. Such lack of therapeutic targets originates, in part, from the incomplete map of the molecular mechanisms underlying cerebrospinal fluid (CSF) secretion by the choroid plexus. Methods: The transcriptomic profile of rat choroid plexus was generated by RNA Sequencing (RNAseq) of whole tissue and epithelial cells captured by fluorescence-activated cell sorting (FACS), and compared to proximal tubules. The bioinformatic analysis comprised mapping to reference genome followed by filtering for type, location, and association with alias and protein function. The transporters and associated regulatory modules were arranged in discovery tables according to their transcriptional abundance and tied together in association network analysis. Results: The transcriptomic profile of choroid plexus displays high similarity between sex and species (human, rat, and mouse) and lesser similarity to another secretory epithelium, the proximal tubules. The discovery tables provide lists of transport mechanisms that could participate in CSF secretion and suggest regulatory candidates. Conclusions: With quantification of the transport protein abundance in choroid plexus and their potentially linked regulatory modules, we envision a molecular tool to devise rational hypotheses regarding future delineation of choroidal transport proteins involved in CSF secretion and their regulation. Our vision is to obtain pharmaceutical targets towards modulation of CSF production in pathologies involving disturbed brain water dynamics.

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“…For example, the clearly defined function of URAT1 is to promote reabsorption of uric acid at the apical membrane of proximal tubule epithelial cells (TECs) ( Enomoto et al, 2002 ). GLUT9 functions as a transporter that reabsorbs both uric acid and glucose into tubular cells ( Chiba et al, 2020 ). Accordingly, the regulation of cellular uric acid transporters would be able to result in alteration in urate excretion in the kidney ( Nakayama et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Basis for Use of a Novel Compound in Hyperuricemia: Anti-Hyperuricemic and Anti-Inflammatory Effects

et al. 2021

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Background: The prevalence of hyperuricemia is considered high worldwide. Hyperuricemia occurs due to decreased excretion of uric acid, increased synthesis of uric acid, or a combination of both mechanisms. There is growing evidence that hyperuricemia is associated with a decline of renal function.Purpose: This study is aimed at investigating the effects of the novel compound on lowering the serum uric acid level and alleviating renal inflammation induced by high uric acid in hyperuricemic mice.Methods: Hyperuricemic mice model was induced by potassium oxonate and used to evaluate the effects of the novel compound named FxUD. Enzyme-linked immunosorbent assay was used to detect the related biochemical markers. Hematoxylin-eosin (HE) staining was applied to observe pathological changes. The mRNA expression levels were tested by qRT-PCR. The protein levels were determined by Western blot. In parallel, human proximal renal tubular epithelial cells (HK-2) derived from normal kidney was used to further validate the anti-inflammatory effects in vitro.Results: FxUD administration significantly decreased serum uric acid levels, restored the kidney function parameters, and improved the renal pathological injury. Meanwhile, treatment with FxUD effectively inhibited serum and liver xanthine oxidase (XOD) levels. Reversed expression alterations of renal inflammatory cytokines, urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were observed in hyperuricemic mice. Western blot results illustrated FxUD down-regulated protein levels of inflammasome components. Further studies showed that FxUD inhibited the activation of NF-κB signaling pathway in the kidney of hyperuricemic mice. In parallel, the anti-inflammatory effect of FxUD was also confirmed in HK-2.Conclusion: Our study reveals that FxUD exhibits the anti-hyperuricemic and anti-inflammatory effects through regulating hepatic XOD and renal urate reabsorption transporters, and suppressing NF-κB/NLRP3 pathway in hyperuricemia. The results provide the evidence that FxUD may be potential for the treatment of hyperuricemia with kidney inflammation.

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Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

Cited by 23 publications

References 176 publications

Immunohistochemical expression of osteopontin and collagens in choroid plexus of human brains

Immunohistochemical expression of osteopontin and collagens in choroid plexus of human brains

Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus

Pharmacological Basis for Use of a Novel Compound in Hyperuricemia: Anti-Hyperuricemic and Anti-Inflammatory Effects

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