Conditionally immortalized brain capillary endothelial cell lines established from a transgenic mouse harboring temperature-sensitive simian virus 40 large T-antigen gene

Bone morphogenetic protein (BMP) signaling is involved in differentiation of neural precursor cells into astrocytes, but its contribution to angiogenesis is not well characterized. This study examines the role of BMP signaling through BMP type IA receptor (BMPRIA) in early neural development using a conditional knockout mouse model, in which Bmpr1a is selectively disrupted in telencephalic neural stem cells. The conditional mutant mice show a significant increase in the number of cerebral blood vessels and the level of vascular endothelial growth factor (VEGF) is significantly upregulated in the mutant astrocytes. The mutant mice also show leakage of immunoglobulin around cerebral microvessels in neonatal mice, suggesting a defect in formation of the blood-brain-barrier. In addition, astrocytic endfeet fail to encircle cortical blood vessels in the mutant mice. These results suggest that BMPRIA signaling in astrocytes regulates the expression of VEGF for proper cerebrovascular angiogenesis and has a role on in the formation of the blood-brain-barrier.

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“…8A). The fact that neurocan lowered adhesion ability of endothelial cell lines TM-BBB (Hosoya et al, 2000) (Fig. 8B) and HUVEC cells (Fig.…”

Section: Glial Bmpria Plays a Critical Role In Formation Of The Bbbmentioning

confidence: 87%

BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood–brain-barrier

Araya

Kudo

Kawano

et al. 2008

Molecular and Cellular Neuroscience

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“…Cell culture A conditionally immortalized mouse brain capillary endothelial cell line (TM-BBB1) was established from transgenic mouse harboring the temperature-sensitive simian virus 40 (ts SV 40) large T-antigen in our laboratory (Hosoya et al 2000). TM-BBB1 cells were routinely grown in collagen type I-coated tissue flasks (Becton Dickinson, Bedford, MA, USA) at 33°C under 5% CO 2 /air.…”

Section: Animalsmentioning

confidence: 99%

“…The brain capillary-rich fraction was collected from brain homogenates as described previously (Hosoya et al 2000). Briefly, the cerebrum was excised from mouse, dissected into 2 mm pieces, and homogenized using a Potter-Elvehjem homogenizer in extracellular fluid buffer containing 10 mM HEPES (pH 7.4), 122 mM NaCl, 25 mM NaHCO 3 , 3 mM KCl, 1.4 mM CaCl 2 , 2 mM MgSO 4 , 0.4 mM K 2 HPO 4 , and 10 mM D-glucose.…”

Section: Western Blot Analysismentioning

confidence: 99%

Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells

Ohtsuki

Takizawa

Takanaga

et al. 2004

Journal of Neurochemistry

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Organic anion transporting polypeptide 3 (oatp3) transports various CNS-acting endogenous compounds, including thyroid hormones and prostaglandin E 2 , between extra-and intracellular spaces, suggesting a possible role in CNS function. The purpose of this study was to clarify the expression and localization of oatp3 in the mouse brain. RT-PCR analysis revealed that oatp3 mRNA is expressed in brain capillary-rich fraction, conditionally immortalized brain capillary endothelial cells, choroid plexus, brain and lung, but not in liver or kidney, where oatp1, 2 and 5 mRNAs were detected. Immunohistochemical analysis with anti-oatp3 antibody suggests that oatp3 protein is localized at the brush-border membrane of mouse choroid plexus epithelial cells. Furthermore, intense immunoreactivity was detected in neural cells in the border region between hypothalamus and thalamus, and in the olfactory bulb. Immunoreactivity was also detected in brain capillary endothelial cells in the cerebral cortex. These localizations in the mouse brain suggest that oatp3 plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells. Keywords: blood-brain barrier, choroid plexus, hypothalamus, olfactory bulb, organic anion transporting polypeptide 3. Organic anion transporting polypeptide 3 (oatp3; Slc21a7) mediates sodium-independent transport of a wide variety of amphipathic organic compounds, including opioid peptides, neurosteroid conjugates, thyroid hormones (THs), bile acids and drugs, such as fexofenadine (Abe et al. 1998;Dresser et al. 2002;Hagenbuch and Meier 2003). Since many of these substrates are active in the CNS, oatp3 may play a role in the control of CNS functions.THs play an important role in normal CNS development and maturation. The expression of TH receptors was detected in adult brain (Puymirat et al. 1991), and hypothyroidism induces changes in the neuronal morphology of adult rat brain (Ruiz-Marcos et al. 1980) and affects memory in human patients (Burmeister et al. 2001). THs interact with nuclear TH receptors to express their effects. Although it was believed that THs enter target cells by passive diffusion, the recent reports have demonstrated that their cellular uptake by cells, including neurons and astrocytes, is carrier-mediated (Francon et al. 1989;Chantoux et al. 1995;Hennemann et al. 2001). Although roles of oatp family members in neural cells have not been considered yet, it is conceivable that oatps mediate TH uptake of the target cells in the brain.Expression of oatp3 mRNA in rat brain has been detected by means of RNase protection assay and RT-PCR analysis (Walters et al. 2000;Ohtsuki et al. 2003). Since oatp3 mediates transport of THs, such as triiodothyronine (T 3 ) and thyroxine (T 4 ) (Abe et al. 1998), we hypothesize that oatp3 is expressed at the neural cells and mediates their TH uptake. Received January 13, 2004; revised manuscript received March 19, 2004; accepted April 8, 2004.Address correspondence ...

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“…Brain capillary endothelial cell lines(TM-BBB) (69) von Willebrand factor, acetylated LDL uptake Kidney tubule cell lines Distal tubule cell line (TKC-2) (3,79) Dome formation, vasopressin-induced cAMP synthesis Early proximal tubule cell line (S1). (80,82) Unique morphology specific to proximal tubule kidney tubule cell lines from microdissected nephron segments (82) Macula densa cell line (83) Neuronal nitric oxide synthase (nNOS)…”

Section: Transport Systems Of the Tissue-blood Barriers The Blood-bramentioning

confidence: 99%

Conditionally immortalized brain capillary endothelial cell lines established from a transgenic mouse harboring temperature-sensitive simian virus 40 large T-antigen gene

Cited by 68 publications

References 32 publications

BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood–brain-barrier

BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood–brain-barrier

Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells

The immortalized cell lines with differentiation potentials: Their establishment and possible application

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