{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts directly mention OR4C46, a review of these studies reveals a unifying theme: the critical regulation of intercellular barrier integrity by key tight junction proteins—most notably claudin‐5, occludin, and other barrier‐associated components—and their dynamic regulation in health and disease. In diverse pathological states ranging from neurodegeneration and neuroinflammation to acute vascular injury and metabolic dysfunction, disruptions in tight junction organization drive leakage across barriers such as the blood–brain barrier, blood–spinal cord barrier, blood–testis barrier, and vascular endothelium. These studies demonstrate that factors including pathogenic mutant proteins, pro‐inflammatory cytokines, matrix metalloproteinases, and altered intracellular signaling cascades can precipitate degradation or mislocalization of junctional proteins, triggering barrier compromise and subsequent tissue injury and inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, detailed investigations have elucidated how alterations in signaling pathways—such as those mediated by NF‑κB, AKT/FOXO1, SMAD3, and even circadian regulators like BMAL1—influence the expression, phosphorylation, and cellular localization of barrier-forming proteins. In parallel, extracellular mediators including transforming growth factor β1, tumor necrosis factor α, and matrix metalloproteinases have been shown to drive internalization or direct proteolysis of claudin‐5 and occludin. Such changes impair barrier function and ultimately contribute to edema formation, increased permeability to inflammatory mediators, and disrupted cellular homeostasis in organs ranging from the brain to the heart and kidneys."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, these investigations extend to advanced models that link barrier dysregulation to inflammatory leukocyte trafficking, neuronal dysfunction, and even cardiac and retinal pathology. Through integrative proteomic, genetic, and in vivo imaging techniques, researchers have highlighted that restoring junctional protein expression can alleviate barrier leakage, providing promising therapeutic avenues. While none of these reports specifically address OR4C46, one may speculate—by analogy with the modulatory roles observed for other membrane proteins—that if OR4C46 were involved in similar cellular contexts, its function might relate to the regulation of barrier integrity and intercellular signaling. Collectively, these studies offer a broad perspective on the molecular determinants of barrier function that could serve as a framework for future inquiry into the roles of less well‐characterized proteins, such as OR4C46, within this complex regulatory network."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kazumasa Morita, Hiroyuki Sasaki, Kyoko Furuse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of claudin-5 in dermal vascular endothelia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1034/j.1600-0625.2003.120309.x"}], "href": "https://doi.org/10.1034/j.1600-0625.2003.120309.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12823443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12823443"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jamie L Sanford, Jonathan D Edwards, Tessily A Mays, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Claudin-5 localizes to the lateral membranes of cardiomyocytes and is altered in utrophin/dystrophin-deficient cardiomyopathic mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2004.11.025"}], "href": "https://doi.org/10.1016/j.yjmcc.2004.11.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15698839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15698839"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Fengshi Chen, Nobuyuki Kondo, Makoto Sonobe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of endothelial cell-specific adhesion molecules in lungs after cardiac arrest."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Interact Cardiovasc Thorac Surg (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1510/icvts.2007.166355"}], "href": "https://doi.org/10.1510/icvts.2007.166355"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18281348"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18281348"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Matthew Campbell, Anna-Sophia Kiang, Paul F Kenna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNAi-mediated reversible opening of the blood-brain barrier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gene Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jgm.1211"}], "href": "https://doi.org/10.1002/jgm.1211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18509865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18509865"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Malgorzata Burek, Carola Y Förster "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and characterization of the murine claudin-5 promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2008.09.041"}], "href": "https://doi.org/10.1016/j.mce.2008.09.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18996436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18996436"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Svetlana M Stamatovic, Richard F Keep, Michael M Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caveolae-mediated internalization of occludin and claudin-5 during CCL2-induced tight junction remodeling in brain endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.000521"}], "href": "https://doi.org/10.1074/jbc.M109.000521"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19423710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19423710"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Carla M K Morrow, Gaurav Tyagi, Liz Simon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Claudin 5 expression in mouse seminiferous epithelium is dependent upon the transcription factor ets variant 5 and contributes to blood-testis barrier function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.109.077040"}], "href": "https://doi.org/10.1095/biolreprod.109.077040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19571261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19571261"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Feng Chen, Norifumi Ohashi, Wensheng Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruptions of occludin and claudin-5 in brain endothelial cells in vitro and in brains of mice with acute liver failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.23203"}], "href": "https://doi.org/10.1002/hep.23203"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19821483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19821483"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Malgorzata Burek, Paula A Arias-Loza, Norbert Roewer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Claudin-5 as a novel estrogen target in vascular endothelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.109.197582"}], "href": "https://doi.org/10.1161/ATVBAHA.109.197582"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19910637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19910637"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jingjing Zhang, Jörg Piontek, Hartwig Wolburg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Establishment of a neuroepithelial barrier by Claudin5a is essential for zebrafish brain ventricular lumen expansion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0911996107"}], "href": "https://doi.org/10.1073/pnas.0911996107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20080584"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20080584"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "An Soo Jang, Vincent J Concel, Kiflai Bein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial dysfunction and claudin 5 regulation during acrolein-induced lung injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2009-0391OC"}], "href": "https://doi.org/10.1165/rcmb.2009-0391OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20525806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20525806"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Karin E Sandoval, Ken A Witt "}, {"type": "b", "children": [{"type": "t", "text": "Age and 17β-estradiol effects on blood-brain barrier tight junction and estrogen receptor proteins in ovariectomized rats."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microvasc Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mvr.2010.12.007"}], "href": "https://doi.org/10.1016/j.mvr.2010.12.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21192956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21192956"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ryo Koda, Linning Zhao, Eishin Yaoita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel expression of claudin-5 in glomerular podocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-010-1117-y"}], "href": "https://doi.org/10.1007/s00441-010-1117-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21271259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21271259"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jasmin Kranz, Ernst Petzinger, Joachim Geyer "}, {"type": "b", "children": [{"type": "t", "text": "Brain penetration of the OAB drug trospium chloride is not increased in aged mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Urol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00345-011-0803-z"}], "href": "https://doi.org/10.1007/s00345-011-0803-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22120415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22120415"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Muhammad Aslam, Nafees Ahmad, Rajneesh Srivastava, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNF-alpha induced NFκB signaling and p65 (RelA) overexpression repress Cldn5 promoter in mouse brain endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cytokine (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cyto.2011.10.016"}], "href": "https://doi.org/10.1016/j.cyto.2011.10.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22138107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22138107"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Weiguo Chen, Rajesh Sharma, Alicia N Rizzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of claudin-5 in the attenuation of murine acute lung injury by simvastatin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2013-0058OC"}], "href": "https://doi.org/10.1165/rcmb.2013-0058OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24028293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24028293"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Malgorzata Burek, Katrin Steinberg, Carola Y Förster "}, {"type": "b", "children": [{"type": "t", "text": "Mechanisms of transcriptional activation of the mouse claudin-5 promoter by estrogen receptor alpha and beta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2014.05.003"}], "href": "https://doi.org/10.1016/j.mce.2014.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24846172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24846172"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Ryan B Camire, Holly J Beaulac, Stephanie A Brule, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biphasic modulation of paracellular claudin-5 expression in mouse brain endothelial cells is mediated through the phosphoinositide-3-kinase/AKT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.114.218339"}], "href": "https://doi.org/10.1124/jpet.114.218339"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25281324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25281324"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Amin Boroujerdi, Jennifer V Welser-Alves, Richard Milner "}, {"type": "b", "children": [{"type": "t", "text": "Matrix metalloproteinase-9 mediates post-hypoxic vascular pruning of cerebral blood vessels by degrading laminin and claudin-5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Angiogenesis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10456-015-9464-7"}], "href": "https://doi.org/10.1007/s10456-015-9464-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25812799"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25812799"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Matthew A McMillin, Gabriel A Frampton, Andrew P Seiwell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TGFβ1 exacerbates blood-brain barrier permeability in a mouse model of hepatic encephalopathy via upregulation of MMP9 and downregulation of claudin-5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/labinvest.2015.70"}], "href": "https://doi.org/10.1038/labinvest.2015.70"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26006017"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26006017"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Jie Liu, John Weaver, Xinchun Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nitric Oxide Interacts with Caveolin-1 to Facilitate Autophagy-Lysosome-Mediated Claudin-5 Degradation in Oxygen-Glucose Deprivation-Treated Endothelial Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Neurobiol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12035-015-9504-8"}], "href": "https://doi.org/10.1007/s12035-015-9504-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26515186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26515186"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Dimitrios Papadopoulos, Raimund Dietze, Mazen Shihan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dehydroepiandrosterone Sulfate Stimulates Expression of Blood-Testis-Barrier Proteins Claudin-3 and -5 and Tight Junction Formation via a Gnα11-Coupled Receptor in Sertoli Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0150143"}], "href": "https://doi.org/10.1371/journal.pone.0150143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26938869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26938869"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Debayon Paul, Valentina Baena, Shujun Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Appearance of claudin-5"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " leukocytes in the central nervous system during neuroinflammation: a novel role for endothelial-derived extracellular vesicles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuroinflammation (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12974-016-0755-8"}], "href": "https://doi.org/10.1186/s12974-016-0755-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27852330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27852330"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Anita Sapoznikov, Yoav Gal, Reut Falach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early disruption of the alveolar-capillary barrier in a ricin-induced ARDS mouse model: neutrophil-dependent and -independent impairment of junction proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00300.2018"}], "href": "https://doi.org/10.1152/ajplung.00300.2018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30382767"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30382767"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Philipp Berndt, Lars Winkler, Jimmi Cording, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tight junction proteins at the blood-brain barrier: far more than claudin-5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-019-03030-7"}], "href": "https://doi.org/10.1007/s00018-019-03030-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30734065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30734065"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Fuhong Liu, Qiang Liu, Fangshu Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Erg mediates downregulation of claudin-5 in the brain endothelium of a murine experimental model of cerebral malaria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.13526"}], "href": "https://doi.org/10.1002/1873-3468.13526"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31271645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31271645"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Tao Liang, Huihui Ju, Yile Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of glycogen synthase kinase 3β improves cognitive function in aged mice by upregulating claudin presences in cerebral endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/abbs/gmaa002"}], "href": "https://doi.org/10.1093/abbs/gmaa002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32141492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32141492"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Slava Rom, Nathan A Heldt, Sachin Gajghate, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyperglycemia and advanced glycation end products disrupt BBB and promote occludin and claudin-5 protein secretion on extracellular microvesicles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-64349-x"}], "href": "https://doi.org/10.1038/s41598-020-64349-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32350344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32350344"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Dylan Krajewski, Debayon Paul, Shujun Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Appearance of claudin-5"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " leukocyte subtypes in the blood and CNS during progression of EAE."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuroinflammation (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12974-021-02328-3"}], "href": "https://doi.org/10.1186/s12974-021-02328-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34933669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34933669"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Yongguo Zhang, Shari Garrett, Robert E Carroll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vitamin D receptor upregulates tight junction protein claudin-5 against colitis-associated tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mucosal Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41385-022-00502-1"}], "href": "https://doi.org/10.1038/s41385-022-00502-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35338345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35338345"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Ning Zhu, Meidan Wei, Linguang Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Claudin-5 relieves cognitive decline in Alzheimer's disease mice through suppression of inhibitory GABAergic neurotransmission."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.204029"}], "href": "https://doi.org/10.18632/aging.204029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35471411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35471411"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Mark Richards, Emmanuel Nwadozi, Sagnik Pal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Claudin5 protects the peripheral endothelial barrier in an organ and vessel-type-specific manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.78517"}], "href": "https://doi.org/10.7554/eLife.78517"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35861713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35861713"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Shuai Jiang, Shuai Liu, Yuxuan Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cardiac-specific overexpression of Claudin-5 exerts protection against myocardial ischemia and reperfusion injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Basis Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2022.166535"}], "href": "https://doi.org/10.1016/j.bbadis.2022.166535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36058416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36058416"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Yosuke Hashimoto, Chris Greene, Arnold Munnich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CLDN5 gene at the blood-brain barrier in health and disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fluids Barriers CNS (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12987-023-00424-5"}], "href": "https://doi.org/10.1186/s12987-023-00424-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36978081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36978081"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Rajiv Sanwal, Victoria Mintsopoulos, Mihails Ditmans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ultrasound-guided transfection of claudin-5 improves lung endothelial barrier function in lung injury without impairing innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00107.2023"}], "href": "https://doi.org/10.1152/ajplung.00107.2023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37310768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37310768"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Peter Baluk, Keisuke Shirakura, Dietmar Vestweber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heterogeneity of endothelial VE-PTP downstream polarization, Tie2 activation, junctional claudin-5, and permeability in the aorta and vena cava."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-023-03844-9"}], "href": "https://doi.org/10.1007/s00441-023-03844-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38032480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38032480"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Elisa Vázquez-Liébanas, Giuseppe Mocci, Weihan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mosaic deletion of claudin-5 reveals rapid non-cell-autonomous consequences of blood-brain barrier leakage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2024.113911"}], "href": "https://doi.org/10.1016/j.celrep.2024.113911"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38446668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38446668"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Yi Zhang, Baihe Chen, Miao Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel function of claudin-5 in maintaining the structural integrity of the heart and its implications in cardiac pathology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Basis Dis (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2024.167274"}], "href": "https://doi.org/10.1016/j.bbadis.2024.167274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38838411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38838411"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Marta Carús-Cadavieco, Sandra González de la Fuente, Inés Berenguer López, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Cldn5 -and increase in Irf7-in the hippocampus and cerebral cortex of diabetic mice at the early symptomatic stage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nutr Diabetes (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41387-024-00325-y"}], "href": "https://doi.org/10.1038/s41387-024-00325-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39147772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39147772"}]}]}]}