Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBDCUPK)

• DOT Name: Tight junction protein ZO-1 (TJP1)
• Synonyms: Tight junction protein 1; Zona occludens protein 1; Zonula occludens protein 1
• Gene Name: TJP1
• Related Disease:
  Cognitive impairment
  Adult lymphoma
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Cardiac failure
  Cardiomyopathy
  Cholestasis
  Chronic kidney disease
  Coeliac disease
  Colorectal neoplasm
  Dilated cardiomyopathy
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Liver cancer
  Lung adenocarcinoma
  Lymphoma
  Lymphoma, non-Hodgkin, familial
  Melanoma
  Narcolepsy
  Neoplasm
  Non-hodgkin lymphoma
  Non-small-cell lung cancer
  Pediatric lymphoma
  Peptic esophagitis
  Plasma cell myeloma
  Subarachnoid hemorrhage
  Thyroid tumor
  Type-1/2 diabetes
  Ulcerative colitis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Uveitis
  Adrenoleukodystrophy
  Encephalitis
  Lung cancer
  Lung carcinoma
  Meningioma
  Small-cell lung cancer
  Arrhythmogenic right ventricular cardiomyopathy
  Asthma
  Brain disease
  Hepatitis C virus infection
  Metastatic malignant neoplasm
  Non-insulin dependent diabetes
  Small lymphocytic lymphoma
• UniProt ID: ZO1_HUMAN
• PDB ID: 2H2B; 2H2C; 2H3M; 2JWE; 2KXR; 2KXS; 2RCZ; 3CYY; 3LH5; 3SHU; 3SHW; 3TSV; 3TSW; 3TSZ; 4OEO; 4OEP; 4Q2Q; 4YYX
• Pfam ID: PF00625 ; PF00595 ; PF07653 ; PF00791
• Sequence:
  MSARAAAAKSTAMEETAIWEQHTVTLHRAPGFGFGIAISGGRDNPHFQSGETSIVISDVL
  KGGPAEGQLQENDRVAMVNGVSMDNVEHAFAVQQLRKSGKNAKITIRRKKKVQIPVSRPD
  PEPVSDNEEDSYDEEIHDPRSGRSGVVNRRSEKIWPRDRSASRERSLSPRSDRRSVASSQ
  PAKPTKVTLVKSRKNEEYGLRLASHIFVKEISQDSLAARDGNIQEGDVVLKINGTVTENM
  SLTDAKTLIERSKGKLKMVVQRDERATLLNVPDLSDSIHSANASERDDISEIQSLASDHS
  GRSHDRPPRRSRSRSPDQRSEPSDHSRHSPQQPSNGSLRSRDEERISKPGAVSTPVKHAD
  DHTPKTVEEVTVERNEKQTPSLPEPKPVYAQVGQPDVDLPVSPSDGVLPNSTHEDGILRP
  SMKLVKFRKGDSVGLRLAGGNDVGIFVAGVLEDSPAAKEGLEEGDQILRVNNVDFTNIIR
  EEAVLFLLDLPKGEEVTILAQKKKDVYRRIVESDVGDSFYIRTHFEYEKESPYGLSFNKG
  EVFRVVDTLYNGKLGSWLAIRIGKNHKEVERGIIPNKNRAEQLASVQYTLPKTAGGDRAD
  FWRFRGLRSSKRNLRKSREDLSAQPVQTKFPAYERVVLREAGFLRPVTIFGPIADVAREK
  LAREEPDIYQIAKSEPRDAGTDQRSSGIIRLHTIKQIIDQDKHALLDVTPNAVDRLNYAQ
  WYPIVVFLNPDSKQGVKTMRMRLCPESRKSARKLYERSHKLRKNNHHLFTTTINLNSMND
  GWYGALKEAIQQQQNQLVWVSEGKADGATSDDLDLHDDRLSYLSAPGSEYSMYSTDSRHT
  SDYEDTDTEGGAYTDQELDETLNDEVGTPPESAITRSSEPVREDSSGMHHENQTYPPYSP
  QAQPQPIHRIDSPGFKPASQQKAEASSPVPYLSPETNPASSTSAVNHNVNLTNVRLEEPT
  PAPSTSYSPQADSLRTPSTEAAHIMLRDQEPSLSSHVDPTKVYRKDPYPEEMMRQNHVLK
  QPAVSHPGHRPDKEPNLTYEPQLPYVEKQASRDLEQPTYRYESSSYTDQFSRNYEHRLRY
  EDRVPMYEEQWSYYDDKQPYPSRPPFDNQHSQDLDSRQHPEESSERGYFPRFEEPAPLSY
  DSRPRYEQAPRASALRHEEQPAPGYDTHGRLRPEAQPHPSAGPKPAESKQYFEQYSRSYE
  QVPPQGFTSRAGHFEPLHGAAAVPPLIPSSQHKPEALPSNTKPLPPPPTQTEEEEDPAMK
  PQSVLTRVKMFENKRSASLETKKDVNDTGSFKPPEVASKPSGAPIIGPKPTSQNQFSEHD
  KTLYRIPEPQKPQLKPPEDIVRSNHYDPEEDEEYYRKQLSYFDRRSFENKPPAHIAASHL
  SEPAKPAHSQNQSNFSSYSSKGKPPEADGVDRSFGEKRYEPIQATPPPPPLPSQYAQPSQ
  PVTSASLHIHSKGAHGEGNSVSLDFQNSLVSKPDPPPSQNKPATFRPPNREDTAQAAFYP
  QKSFPDKAPVNGTEQTQKTVTPAYNRFTPKPYTSSARPFERKFESPKFNHNLLPSETAHK
  PDLSSKTPTSPKTLVKSHSLAQPPEFDSGVETFSIHAEKPKYQINNISTVPKAIPVSPSA
  VEEDEDEDGHTVVATARGIFNSNGGVLSSIETGVSIIIPQGAIPEGVEQEIYFKVCRDNS
  ILPPLDKEKGETLLSPLVMCGPHGLKFLKPVELRLPHCDPKTWQNKCLPGDPNYLVGANC
  VSVLIDHF
• Function: TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton. The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation. Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells. Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling. With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus.
• Tissue Specificity: The alpha-containing isoform is found in most epithelial cell junctions. The short isoform is found both in endothelial cells and the highly specialized epithelial junctions of renal glomeruli and Sertoli cells of the seminiferous tubules.
• KEGG Pathway:
  Adherens junction (hsa04520)
  Tight junction (hsa04530)
  Gap junction (hsa04540)
  Vibrio cholerae infection (hsa05110)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Pathogenic Escherichia coli infection (hsa05130)
• Reactome Pathway:
  Signaling by Hippo (R-HSA-2028269)
  Apoptotic cleavage of cell adhesion proteins (R-HSA-351906)
  RUNX1 regulates expression of components of tight junctions (R-HSA-8935964)
  SARS-CoV-2 targets PDZ proteins in cell-cell junction (R-HSA-9705677)
  Regulation of gap junction activity (R-HSA-191650)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Altered Expression	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[6]
Cardiac failure	DISDC067	Strong	Altered Expression	[7]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[8]
Cholestasis	DISDJJWE	Strong	Biomarker	[9]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[10]
Coeliac disease	DISIY60C	Strong	Altered Expression	[11]
Colorectal neoplasm	DISR1UCN	Strong	Posttranslational Modification	[12]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[15]
Liver cancer	DISDE4BI	Strong	Altered Expression	[6]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[16]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[17]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[18]
Neoplasm	DISZKGEW	Strong	Altered Expression	[19]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[20]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Peptic esophagitis	DISJSGBZ	Strong	Biomarker	[21]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[22]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Altered Expression	[23]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[24]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[25]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[15]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Uveitis	DISV0RYS	Strong	Biomarker	[26]
Adrenoleukodystrophy	DISTUD1F	moderate	Altered Expression	[27]
Encephalitis	DISLD1RL	moderate	Biomarker	[28]
Lung cancer	DISCM4YA	moderate	Altered Expression	[29]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[29]
Meningioma	DISPT4TG	moderate	Altered Expression	[30]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[31]
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	Limited	Autosomal dominant	[32]
Asthma	DISW9QNS	Limited	Altered Expression	[33]
Brain disease	DIS6ZC3X	Limited	Biomarker	[34]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[35]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[19]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[36]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[37]

34 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Tight junction protein ZO-1 (TJP1).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tight junction protein ZO-1 (TJP1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tight junction protein ZO-1 (TJP1).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tight junction protein ZO-1 (TJP1).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tight junction protein ZO-1 (TJP1).	[42]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tight junction protein ZO-1 (TJP1).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Tight junction protein ZO-1 (TJP1).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tight junction protein ZO-1 (TJP1).	[45]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tight junction protein ZO-1 (TJP1).	[46]
Marinol	DM70IK5	Approved	Marinol increases the expression of Tight junction protein ZO-1 (TJP1).	[47]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Tight junction protein ZO-1 (TJP1).	[48]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Tight junction protein ZO-1 (TJP1).	[49]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Tight junction protein ZO-1 (TJP1).	[50]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Tight junction protein ZO-1 (TJP1).	[45]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Tight junction protein ZO-1 (TJP1).	[51]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Tight junction protein ZO-1 (TJP1).	[52]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Tight junction protein ZO-1 (TJP1).	[53]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Tight junction protein ZO-1 (TJP1).	[54]
Clopidogrel	DMOL54H	Approved	Clopidogrel decreases the expression of Tight junction protein ZO-1 (TJP1).	[56]
Telmisartan	DMS3GX2	Phase 3 Trial	Telmisartan decreases the expression of Tight junction protein ZO-1 (TJP1).	[58]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tight junction protein ZO-1 (TJP1).	[60]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Tight junction protein ZO-1 (TJP1).	[63]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tight junction protein ZO-1 (TJP1).	[64]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tight junction protein ZO-1 (TJP1).	[53]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tight junction protein ZO-1 (TJP1).	[65]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Tight junction protein ZO-1 (TJP1).	[67]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Tight junction protein ZO-1 (TJP1).	[68]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Tight junction protein ZO-1 (TJP1).	[44]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Tight junction protein ZO-1 (TJP1).	[69]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Tight junction protein ZO-1 (TJP1).	[70]
Lead acetate	DML0GZ2	Investigative	Lead acetate decreases the expression of Tight junction protein ZO-1 (TJP1).	[71]
PATULIN	DM0RV9C	Investigative	PATULIN decreases the expression of Tight junction protein ZO-1 (TJP1).	[72]
OXYRESVERATROL	DMN7S4L	Investigative	OXYRESVERATROL increases the expression of Tight junction protein ZO-1 (TJP1).	[73]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Investigative	2-Methylamino-succinic acid(NMDA) decreases the expression of Tight junction protein ZO-1 (TJP1).	[74]

5 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the localization of Tight junction protein ZO-1 (TJP1).	[55]
Olmesartan medoxomil	DMWBHRY	Approved	Olmesartan medoxomil affects the localization of Tight junction protein ZO-1 (TJP1).	[57]
Phenol	DM1QSM3	Phase 2/3	Phenol affects the localization of Tight junction protein ZO-1 (TJP1).	[59]
PMID26560530-Compound-35	DMO36RL	Patented	PMID26560530-Compound-35 affects the localization of Tight junction protein ZO-1 (TJP1).	[62]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde affects the localization of Tight junction protein ZO-1 (TJP1).	[66]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Tight junction protein ZO-1 (TJP1).	[61]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Tight junction protein ZO-1 (TJP1).	[61]

References

• [1] Protective effect of S-nitrosoglutathione administration against hyperglycemia induced disruption of blood brain barrier is mediated by modulation of tight junction proteins and cell adhesion molecules.Neurochem Int. 2018 Sep;118:205-216. doi: 10.1016/j.neuint.2018.05.009. Epub 2018 May 21.
• [2] Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients.Oncol Rep. 2013 Jul;30(1):455-61. doi: 10.3892/or.2013.2450. Epub 2013 May 10.
• [3] Tight Junction Protein 1 Dysfunction Contributes to Cell Motility in Bladder Cancer.Anticancer Res. 2018 Aug;38(8):4607-4615. doi: 10.21873/anticanres.12765.
• [4] Loss of the tight junction MAGUK ZO-1 in breast cancer: relationship to glandular differentiation and loss of heterozygosity.Am J Pathol. 1998 Dec;153(6):1767-73. doi: 10.1016/S0002-9440(10)65691-X.
• [5] Enhanced tight junction function in human breast cancer cells by antioxidant, selenium and polyunsaturated lipid.J Cell Biochem. 2007 May 1;101(1):155-66. doi: 10.1002/jcb.21162.
• [6] Decreased expression of ZO-1 is associated with tumor metastases in liver cancer.Oncol Lett. 2019 Feb;17(2):1859-1864. doi: 10.3892/ol.2018.9765. Epub 2018 Nov 27.
• [7] Gap junction remodelling in human heart failure is associated with increased interaction of connexin43 with ZO-1.Cardiovasc Res. 2008 Mar 1;77(4):757-65. doi: 10.1093/cvr/cvm083. Epub 2007 Dec 4.
• [8] Whole-Exome Sequencing Identifies Pathogenic Variants in TJP1 Gene Associated With Arrhythmogenic Cardiomyopathy.Circ Genom Precis Med. 2018 Oct;11(10):e002123. doi: 10.1161/CIRCGEN.118.002123.
• [9] Bile duct ligation in the rat causes upregulation of ZO-2 and decreased colocalization of claudins with ZO-1 and occludin.Histochem Cell Biol. 2008 Mar;129(3):289-99. doi: 10.1007/s00418-007-0374-7. Epub 2008 Jan 15.
• [10] Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions.Toxins (Basel). 2018 Oct 7;10(10):404. doi: 10.3390/toxins10100404.
• [11] Lower expression of tight junction protein 1 gene and increased FOXP3 expression in the small bowel mucosa in coeliac disease and associated type 1 diabetes mellitus.Int Arch Allergy Immunol. 2011;156(4):451-61. doi: 10.1159/000324456. Epub 2011 Aug 10.
• [12] Redifferentiation and ZO-1 reexpression in liver-metastasized colorectal cancer: possible association with epidermal growth factor receptor-induced tyrosine phosphorylation of ZO-1.Cancer Sci. 2003 Feb;94(2):166-72. doi: 10.1111/j.1349-7006.2003.tb01414.x.
• [13] miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer.Cell Death Dis. 2018 Nov 8;9(11):1123. doi: 10.1038/s41419-018-1093-9.
• [14] Increased systemic zonula occludens 1 associated with inflammation and independent biomarker in patients with hepatocellular carcinoma.BMC Cancer. 2018 May 18;18(1):572. doi: 10.1186/s12885-018-4484-5.
• [15] Genetic variation and expression levels of tight junction genes identifies association between MAGI3 and inflammatory bowel disease.BMC Gastroenterol. 2017 May 25;17(1):68. doi: 10.1186/s12876-017-0620-y.
• [16] A functional variant in miR-155 regulation region contributes to lung cancer risk and survival.Oncotarget. 2015 Dec 15;6(40):42781-92. doi: 10.18632/oncotarget.5840.
• [17] Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion.Am J Pathol. 2005 May;166(5):1541-54. doi: 10.1016/S0002-9440(10)62370-X.
• [18] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [19] Asparaginyl endopeptidase induces endothelial permeability and tumor metastasis via downregulating zonula occludens protein ZO-1.Biochim Biophys Acta Mol Basis Dis. 2019 Sep 1;1865(9):2267-2275. doi: 10.1016/j.bbadis.2019.05.003. Epub 2019 May 13.
• [20] Increased ZO-1 expression predicts valuable prognosis in non-small cell lung cancer.Int J Clin Exp Pathol. 2013 Nov 15;6(12):2887-95. eCollection 2013.
• [21] Interleukin-6, desmosome and tight junction protein expression levels in reflux esophagitis-affected mucosa.World J Gastroenterol. 2009 Aug 7;15(29):3621-30. doi: 10.3748/wjg.15.3621.
• [22] Tight Junction Protein 1 Modulates Proteasome Capacity and Proteasome Inhibitor Sensitivity in Multiple Myeloma via EGFR/JAK1/STAT3 Signaling.Cancer Cell. 2016 May 9;29(5):639-652. doi: 10.1016/j.ccell.2016.03.026. Epub 2016 Apr 28.
• [23] Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.Mol Neurobiol. 2019 Feb;56(2):976-985. doi: 10.1007/s12035-018-1145-2. Epub 2018 May 31.
• [24] Tight junctions in thyroid carcinogenesis: diverse expression of claudin-1, claudin-4, claudin-7 and occludin in thyroid neoplasms.Mod Pathol. 2008 Jan;21(1):22-30. doi: 10.1038/modpathol.3800959. Epub 2007 Oct 26.
• [25] Faecalibacterium prausnitzii-derived microbial anti-inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression.J Diabetes. 2020 Mar;12(3):224-236. doi: 10.1111/1753-0407.12986. Epub 2019 Oct 30.
• [26] The corneal endothelium in an endotoxin-induced uveitis model: correlation between in vivo confocal microscopy and immunohistochemistry.Mol Vis. 2008 Jun 16;14:1149-56.
• [27] Effect of alcohol on miR-212 expression in intestinal epithelial cells and its potential role in alcoholic liver disease.Alcohol Clin Exp Res. 2008 Feb;32(2):355-64. doi: 10.1111/j.1530-0277.2007.00584.x. Epub 2007 Dec 21.
• [28] Dysregulation of sonic hedgehog pathway and pericytes in the brain after lentiviral infection.J Neuroinflammation. 2019 Apr 13;16(1):86. doi: 10.1186/s12974-019-1463-y.
• [29] Tight junction protein 1 is regulated by transforming growth factor- and contributes to cell motility in NSCLC cells.BMB Rep. 2015 Feb;48(2):115-20. doi: 10.5483/bmbrep.2015.48.2.035.
• [30] Altered expression of E-Cadherin-related transcription factors indicates partial epithelial-mesenchymal transition in aggressive meningiomas.J Neurol Sci. 2017 Sep 15;380:112-121. doi: 10.1016/j.jns.2017.07.009. Epub 2017 Jul 8.
• [31] Tumor cell heterogeneity in Small Cell Lung Cancer (SCLC): phenotypical and functional differences associated with Epithelial-Mesenchymal Transition (EMT) and DNA methylation changes.PLoS One. 2014 Jun 24;9(6):e100249. doi: 10.1371/journal.pone.0100249. eCollection 2014.
• [32] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [33] Altered expression of epithelial junctional proteins in atopic asthma: possible role in inflammation.Can J Physiol Pharmacol. 2008 Mar;86(3):105-12. doi: 10.1139/y08-004.
• [34] Matrix metalloproteinases inhibition provides neuroprotection against hypoxia-ischemia in the developing brain.J Neurochem. 2009 Nov;111(3):726-36. doi: 10.1111/j.1471-4159.2009.06362.x. Epub 2009 Aug 27.
• [35] The tight junction-associated protein occludin is required for a postbinding step in hepatitis C virus entry and infection.J Virol. 2009 Aug;83(16):8012-20. doi: 10.1128/JVI.00038-09. Epub 2009 Jun 10.
• [36] Evaluation of tight junction protein 1 encoding zona occludens 1 as a candidate gene for albuminuria in a Mexican American population.Exp Clin Endocrinol Diabetes. 2006 Sep;114(8):432-7. doi: 10.1055/s-2006-924328.
• [37] ZO-1 expression shows prognostic value in chronic B cell leukemia.Immunobiology. 2016 Jan;221(1):6-11. doi: 10.1016/j.imbio.2015.08.008. Epub 2015 Aug 17.
• [38] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [39] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [40] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [41] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [42] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [43] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [44] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [45] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [46] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [47] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [48] Vitamin K3 (menadione) suppresses epithelial-mesenchymal-transition and Wnt signaling pathway in human colorectal cancer cells. Chem Biol Interact. 2019 Aug 25;309:108725. doi: 10.1016/j.cbi.2019.108725. Epub 2019 Jun 22.
• [49] Cannabidiol induces osteoblast differentiation via angiopoietin1 and p38 MAPK. Environ Toxicol. 2020 Dec;35(12):1318-1325. doi: 10.1002/tox.22996. Epub 2020 Jul 13.
• [50] Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: a combined in vivo and in vitro approach. PLoS One. 2014 Sep 16;9(9):e107421. doi: 10.1371/journal.pone.0107421. eCollection 2014.
• [51] Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines. Int J Cancer. 2009 Jan 1;124(1):36-45. doi: 10.1002/ijc.23894.
• [52] Polyphenols protect the epithelial barrier function of Caco-2 cells exposed to indomethacin through the modulation of occludin and zonula occludens-1 expression. J Agric Food Chem. 2013 Jun 5;61(22):5291-7. doi: 10.1021/jf400150p. Epub 2013 May 23.
• [53] Prevention of murine experimental corneal trauma by epigenetic events regulating claudin 6 and claudin 9. Jpn J Ophthalmol. 2008 May-Jun;52(3):195-203. doi: 10.1007/s10384-008-0524-z. Epub 2008 Jul 27.
• [54] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [55] Hydrocortisone enhances the barrier properties of HBMEC/ci, a brain microvascular endothelial cell line, through mesenchymal-to-endothelial transition-like effects. Fluids Barriers CNS. 2015 Mar 5;12:7. doi: 10.1186/s12987-015-0003-0. eCollection 2015.
• [56] Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation. Toxicology. 2013 Feb 8;304:41-8. doi: 10.1016/j.tox.2012.11.020. Epub 2012 Dec 7.
• [57] Immunopathogenesis of olmesartan-associated enteropathy. Aliment Pharmacol Ther. 2015 Dec;42(11-12):1303-14. doi: 10.1111/apt.13413. Epub 2015 Oct 1.
• [58] Telmisartan increases the permeability of endothelial cells through zonula occludens-1. Biol Pharm Bull. 2009 Mar;32(3):416-20. doi: 10.1248/bpb.32.416.
• [59] Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization. Toxicol Appl Pharmacol. 2009 Nov 15;241(1):61-70. doi: 10.1016/j.taap.2009.08.002. Epub 2009 Aug 11.
• [60] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [61] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [62] Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells. J Nutr. 2009 May;139(5):965-74. doi: 10.3945/jn.108.100867. Epub 2009 Mar 18.
• [63] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [64] Bisphenol A stimulates the epithelial mesenchymal transition of estrogen negative breast cancer cells via FOXA1 signals. Arch Biochem Biophys. 2015 Nov 1;585:10-16. doi: 10.1016/j.abb.2015.09.006. Epub 2015 Sep 9.
• [65] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [66] Role of phospholipase Cgamma-induced activation of protein kinase Cepsilon (PKCepsilon) and PKCbetaI in epidermal growth factor-mediated protection of tight junctions from acetaldehyde in Caco-2 cell monolayers. J Biol Chem. 2008 Feb 8;283(6):3574-3583. doi: 10.1074/jbc.M709141200. Epub 2007 Nov 8.
• [67] HIF-1 regulates EMT via the Snail and -catenin pathways in paraquat poisoning-induced early pulmonary fibrosis. J Cell Mol Med. 2016 Apr;20(4):688-97. doi: 10.1111/jcmm.12769. Epub 2016 Jan 19.
• [68] HIF-1 is involved in high glucose-induced paracellular permeability of brain endothelial cells. Cell Mol Life Sci. 2012 Jan;69(1):115-28. doi: 10.1007/s00018-011-0731-5. Epub 2011 May 27.
• [69] The marine biotoxin okadaic acid affects intestinal tight junction proteins in human intestinal cells. Toxicol In Vitro. 2019 Aug;58:150-160. doi: 10.1016/j.tiv.2019.03.033. Epub 2019 Mar 26.
• [70] Effect of cytokines on ICAM-1 and ZO-1 expression on human airway epithelial cells. Cell Biol Int. 2005 Sep;29(9):768-77. doi: 10.1016/j.cellbi.2005.05.002.
• [71] [Changes and regulatory mechanism of tight junction proteins in in vitro model of lead-induced blood-brain barrier injury]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013 Nov;29(11):1141-6.
• [72] The mycotoxin patulin, modulates tight junctions in caco-2 cells. Toxicol In Vitro. 2009 Feb;23(1):83-9. doi: 10.1016/j.tiv.2008.10.009. Epub 2008 Oct 29.
• [73] Oxyresveratrol improves tight junction integrity through the PKC and MAPK signaling pathways in Caco-2?cells. Food Chem Toxicol. 2017 Oct;108(Pt A):203-213. doi: 10.1016/j.fct.2017.08.002. Epub 2017 Aug 2.
• [74] N-methyl-D-aspartic acid increases tight junction protein destruction in brain endothelial cell via caveolin-1-associated ERK1/2 signaling. Toxicology. 2022 Mar 30;470:153139. doi: 10.1016/j.tox.2022.153139. Epub 2022 Mar 4.