Adrenomedullin Improves the Blood–Brain Barrier Function Through the Expression of Claudin-5

Honda, Masaru; Nakagawa, Shinsuke; Hayashi, Kentarō; Kitagawa, Naoki; Tsutsumi, Keisuke; Nagata, Izumi; Níwa, Masami

doi:10.1007/s10571-006-9028-x

Cited by 80 publications

(59 citation statements)

References 39 publications

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“…There was no significant change in TEER when we cultured the BBB model up to 10 days after the cells became confluent. The TEER values of the BBB model in our study are comparable to other studies using BMVEC, 22,26 similar to rat BMVEC cells, 24 slightly lower than human BMVEC, 21 but higher than feline BMVEC. 23 Clearly, the TEER is different for different cell types.…”

Section: Discussionsupporting

confidence: 88%

“…In addition, it has been shown that TEER can be modulated by many factors such as cytokines, cAMP, cGMP, nitric oxide, heat and coculturing with other cells. 21,22,[24][25][26] Currently, no specific receptor has been identified for MTf. Although human MTf shares 39% homology with human serum transferrin, 13 TfR is found not to be responsible for MTf transcytosis.…”

Section: Discussionmentioning

confidence: 99%

“…TEER reflects impedance of the passage of small ions through the physiological barrier, and has been widely used to measure BBB integrity. [21][22][23][24][25] Transcytosis assays were performed when the TEER of each BBB model reached the maximal value, which mostly were in the range of 100-150 O cm 2 .…”

Section: Ad5 Transcytosis Mediated By Scar-mtfmentioning

confidence: 99%

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Directing adenovirus across the blood–brain barrier via melanotransferrin (P97) transcytosis pathway in an in vitro model

et al. 2006

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Adenovirus serotype 5 (Ad5) is widely used in the development of gene therapy protocols. However, current gene therapy strategies involving brain are mostly based on intracranial injection. A major obstacle for systemically administered vectors to infect brain tissue is the blood-brain barrier (BBB). One strategy to cross the BBB is transcytosis, a transcellular transport process that shuttles a molecule from one side of the cell to the other side. Recently, melanotransferrin (MTf)/P97 was found to be able to cross the BBB and accumulate in brain. We thus hypothesize that re-directing Ad5 vectors to the MTf transcytosis pathway may facilitate Ad5 vectors to cross the BBB. To test this hypothesis, we constructed a bi-specific adaptor protein containing the extracellular domain of the coxsackie-adenovirus receptor (CAR) and the full-length melanotransferrin (sCAR-MTf), and investigated its ability to re-direct Ad5 vectors to the MTf transcytosis pathway. We found this adaptor protein could redirect Ad5 to the MTf transcytosis pathway in an in vitro BBB model, and the transcytosed Ad5 viral particles retained their native infectivity. The sCAR-MTf-mediated Ad5 transcytosis was temperature-and dose dependent. In addition, we examined the directionality of sCAR-MTf-mediated Ad5 transcytosis, and found the efficiency of apical-to-basal transcytosis was much higher than that of basal-to-apical direction, supporting a role of this strategy in transporting Ad5 vectors towards the brain. Taken together, our study demonstrated that re-directing Ad5 to the MTf transcytosis pathway could facilitate gene delivery across the BBB.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Directing adenovirus across the blood–brain barrier via melanotransferrin (P97) transcytosis pathway in an in vitro model

et al. 2006

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“…In addition, our results indicated that TR-BNBs, which express claudin-5 at cell-cell boundaries, have significantly higher TEER than HUVECs as well as TR-BBBs, which do not express claudin-5 (Ohtsuki et al, 2007). Interestingly, Honda et al reported that adrenomedullin increased the TEER of rat BMEC monolayer through the expression of claudin-5 (Honda et al, 2006). These data and our results indicate that claudin-5 might be a key molecule in maintaining the integrity of TJs in BNB as well as BBB, and malfunction of this molecule might lead to the breakdown of BNB in many autoimmune peripheral neuropathies.…”

Section: Discussionmentioning

confidence: 50%

Endothelial Cells Constituting Blood-nerve Barrier Have Highly Specialized Characteristics as Barrier-forming Cells

Sano

Shimizu

Nakayama

et al. 2007

Cell Struct. Funct.

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ABSTRACT. In autoimmune disorders of the peripheral nervous system (PNS) such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, breakdown of the blood-nerve barrier (BNB) has been considered as a key step in the disease process. Hence, it is important to know the cellular property of peripheral nerve microvascular endothelial cells (PnMECs) constituting the bulk of BNB. Although many in vitro models of the blood-brain barrier (BBB) have been established, very few in vitro BNB models have been reported so far. We isolated PnMECs from transgenic rats harboring the temperature-sensitive SV40 large T-antigen gene (tsA58 rat) and investigated the properties of these "barrier-forming cells". Isolated PnMECs (TR-BNBs) showed high transendothelial electrical resistance and expressed tight junction components and various types of influx as well as efflux transporters that have been reported to function at BBB. Furthermore, we confirmed the in vivo expression of various BBB-forming endothelial cell markers in the endoneurium of a rat sciatic nerve. These results suggest that PnMECs constituting the bulk of BNB have a highly specialized characteristic resembling the endothelial cells forming BBB.

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“…The effect of forskolin on brain endothelial cells was also confirmed by other studies [91,92]. Calcitonin generelated peptide and parathyroid hormone [65] and adrenomedullin [32,93] also clearly demonstrated a cAMPlike effect. The permeability decreasing effect of cAMP analogs was more pronounced in the presence of PDE inhibitors theophylline, methylisobutylxanthine, rolipram, or RO-20-1724 [57].…”

Section: Cyclic Amp Pathwaysupporting

confidence: 74%

Protection of the blood-brain barrier under pathological conditions

Andrea

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Adrenomedullin Improves the Blood–Brain Barrier Function Through the Expression of Claudin-5

Abstract: AM therefore inhibits the paracellular transport in a BBB in vitro model through claudin-5 overexpression.

Cited by 80 publications

References 39 publications

Directing adenovirus across the blood–brain barrier via melanotransferrin (P97) transcytosis pathway in an in vitro model

Directing adenovirus across the blood–brain barrier via melanotransferrin (P97) transcytosis pathway in an in vitro model

Endothelial Cells Constituting Blood-nerve Barrier Have Highly Specialized Characteristics as Barrier-forming Cells

Protection of the blood-brain barrier under pathological conditions

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