The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Occludin as direct target for glucocorticoid‐induced improvement of blood–brain barrier properties in a murine in vitro system
Abstract
Homeostasis of the central nervous system (CNS) microenvironment is essential for its normal function. It is maintained by the blood–brain barrier (BBB) which regulates the transport of molecules from blood into brain and backwards. The integrity of the BBB is compromised in many disorders of the human CNS; therapeutical strategies for several of these diseases include treatment with glucocorticoids, but the molecular basis of how glucocorticoids regulate BBB permeability is not understood. Here, we report the generation and characterization of a murine immortalized brain (cerebral) capillary endothelial (cEND) cell line which expresses the BBB marker occludin at intercellular tight junctions (TJ). Hydrocortisone at physiological concentrations induced upregulation of occludin, accompanied by a threefold enhancement of transendothelial electrical resistance to values up to 1000 Ωcm 2. Insulin enhanced the glucocorticoid response. At the molecular level, hydrocortisone induces increase of occludin at protein and mRNA levels by activation of the glucocorticoid receptor (GR) and its binding to putative glucocorticoid responsive elements in the occludin promoter. At the same time, insulin potentiated the ligand‐dependent GR transactivation via induction of the GR in this in vitro system. This study thus provides insights into the molecular processes of barrier genesis, and may help to elucidate mechanisms of brain pathology at the microvascular level.
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Citations
Cites
Gene regulation by steroid hormones
Beato, M. (1989) · Cell · doi:10.1016/0092-8674(89)90237-7 · Cited by 3,383
Electrical resistance of brain microvascular endothelium
Crone, C., & Olesen, S. P. (1982) · Brain Research · doi:10.1016/0006-8993(82)91227-6 · Cited by 491
Cited by
Helms, H. C., Abbott, N. J., Burek, M., Cecchelli, R., Couraud, P.-O., Deli, M. A., Förster, C., Galla, H. J., Romero, I. A., Shusta, E. V., et al. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16630991 · Cited by 843
Self-citationBlood–Brain Barrier Pathology in Alzheimer's and Parkinson's Disease: Implications for Drug Therapy
Desai, B. S., Monahan, A. J., Carvey, P. M., & Hendey, B. (2007) · Cell Transplantation · doi:10.3727/000000007783464731 · Cited by 339
Liu, W., Wang, Z., Zhang, L., Wei, X., & Li, L. (2012) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2012.00340.x · Cited by 259
Cytokine Signaling Modulates Blood-Brain Barrier Function
Pan, W., P. Stone, K., Hsuchou, H., K. Manda, V., Zhang, Y., & J. Kastin, A. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798220918 · Cited by 241
A Genomic Comparison of in vivo and in vitro Brain Microvascular Endothelial Cells
Calabria, A. R., & Shusta, E. V. (2008) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600518 · Cited by 109
Metadata
- Authors
- Förster, C., Silwedel, C., Golenhofen, N., Burek, M., Kietz, S., Mankertz, J., & Drenckhahn, D.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2005-06
- Volume
- 565
- Issue
- 2
- Pages
- 475-486
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- OpenAlex
- W1905392838
- Cited by
- 214
- References
- 2
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Förster, C., Silwedel, C., Golenhofen, N., Burek, M., Kietz, S., Mankertz, J., & Drenckhahn, D. (2005). Occludin as direct target for glucocorticoid‐induced improvement of blood–brain barrier properties in a murine in vitro system. The Journal of Physiology. https://doi.org/10.1113/jphysiol.2005.084038
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