Details of Drug Off-Target (DOT)

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

• DOT Name: Occludin (OCLN)
• Gene Name: OCLN
• Related Disease:
  Fetal growth restriction
  Glioma
  Rheumatoid arthritis
  46,XY sex reversal 2
  Acute kidney injury
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  B-cell neoplasm
  Bacteremia
  Benign neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cerebral cavernous malformation
  Cervical cancer
  Cervical carcinoma
  Charcot-Marie-Tooth disease type 3
  Clear cell renal carcinoma
  Colorectal carcinoma
  Diabetic retinopathy
  Gastric cancer
  Hepatic veno-occlusive disease
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Multiple sclerosis
  Nervous system inflammation
  Pseudo-TORCH syndrome 1
  Retinopathy
  Schizophrenia
  Stomach cancer
  Subarachnoid hemorrhage
  Ulcerative colitis
  Leukemia
  Pseudo-TORCH syndrome
  Adenocarcinoma
  Carcinoma
  Chronic kidney disease
  Colitis
  Epithelial ovarian cancer
  Ovarian cancer
  Stroke
  Type-1/2 diabetes
• UniProt ID: OCLN_HUMAN
• PDB ID: 1WPA; 1XAW; 3G7C
• Pfam ID: PF01284 ; PF07303
• Sequence:
  MSSRPLESPPPYRPDEFKPNHYAPSNDIYGGEMHVRPMLSQPAYSFYPEDEILHFYKWTS
  PPGVIRILSMLIIVMCIAIFACVASTLAWDRGYGTSLLGGSVGYPYGGSGFGSYGSGYGY
  GYGYGYGYGGYTDPRAAKGFMLAMAAFCFIAALVIFVTSVIRSEMSRTRRYYLSVIIVSA
  ILGIMVFIATIVYIMGVNPTAQSSGSLYGSQIYALCNQFYTPAATGLYVDQYLYHYCVVD
  PQEAIAIVLGFMIIVAFALIIFFAVKTRRKMDRYDKSNILWDKEHIYDEQPPNVEEWVKN
  VSAGTQDVPSPPSDYVERVDSPMAYSSNGKVNDKRFYPESSYKSTPVPEVVQELPLTSPV
  DDFRQPRYSSGGNFETPSKRAPAKGRAGRSKRTEQDHYETDYTTGGESCDELEEDWIREY
  PPITSDQQRQLYKRNFDTGLQEYKSLQSELDEINKELSRLDKELDDYREESEEYMAAADE
  YNRLKQVKGSADYKSKKNHCKQLKSKLSHIKKMVGDYDRQKT
• Function: May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions; (Microbial infection) Acts as a coreceptor for hepatitis C virus (HCV) in hepatocytes.
• Tissue Specificity: Localized at tight junctions of both epithelial and endothelial cells. Highly expressed in kidney. Not detected in testis.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Tight junction (hsa04530)
  Leukocyte transendothelial migration (hsa04670)
  Pathogenic Escherichia coli infection (hsa05130)
  Hepatitis C (hsa05160)
• Reactome Pathway:
  RUNX1 regulates expression of components of tight junctions (R-HSA-8935964)
  Apoptotic cleavage of cell adhesion proteins (R-HSA-351906)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fetal growth restriction	DIS5WEJ5	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Altered Expression	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[3]
46,XY sex reversal 2	DIS0USUN	Strong	Biomarker	[4]
Acute kidney injury	DISXZG0T	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[8]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[8]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[9]
Bacteremia	DIS6N9RZ	Strong	Altered Expression	[10]
Benign neoplasm	DISDUXAD	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[12]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[12]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[13]
Cerebral cavernous malformation	DISLKNYA	Strong	Altered Expression	[14]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[6]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[6]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Strong	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[15]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[16]
Diabetic retinopathy	DISHGUJM	Strong	Altered Expression	[17]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[18]
Hepatic veno-occlusive disease	DISAIU45	Strong	Biomarker	[19]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[20]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[21]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[22]
Lung cancer	DISCM4YA	Strong	Biomarker	[23]
Lung carcinoma	DISTR26C	Strong	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[24]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[25]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[26]
Pseudo-TORCH syndrome 1	DISABKQO	Strong	Autosomal recessive	[27]
Retinopathy	DISB4B0F	Strong	Altered Expression	[28]
Schizophrenia	DISSRV2N	Strong	Biomarker	[29]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[18]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Altered Expression	[30]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[31]
Leukemia	DISNAKFL	moderate	Altered Expression	[32]
Pseudo-TORCH syndrome	DISM9N8Y	Supportive	Autosomal recessive	[27]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[33]
Carcinoma	DISH9F1N	Limited	Altered Expression	[34]
Chronic kidney disease	DISW82R7	Limited	Altered Expression	[35]
Colitis	DISAF7DD	Limited	Altered Expression	[36]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[37]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[37]
Stroke	DISX6UHX	Limited	Altered Expression	[38]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Occludin (OCLN).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Occludin (OCLN).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Occludin (OCLN).	[42]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Occludin (OCLN).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Occludin (OCLN).	[45]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Occludin (OCLN).	[46]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Occludin (OCLN).	[47]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Occludin (OCLN).	[48]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Occludin (OCLN).	[49]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Occludin (OCLN).	[50]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Occludin (OCLN).	[51]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Occludin (OCLN).	[52]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Occludin (OCLN).	[50]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Occludin (OCLN).	[53]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Occludin (OCLN).	[54]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Occludin (OCLN).	[55]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine increases the expression of Occludin (OCLN).	[56]
Clopidogrel	DMOL54H	Approved	Clopidogrel decreases the expression of Occludin (OCLN).	[57]
Thioguanine	DM7NKEV	Approved	Thioguanine decreases the activity of Occludin (OCLN).	[19]
Glycine	DMIOZ29	Approved	Glycine decreases the expression of Occludin (OCLN).	[59]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Occludin (OCLN).	[60]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Occludin (OCLN).	[11]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine increases the expression of Occludin (OCLN).	[56]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Occludin (OCLN).	[60]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Occludin (OCLN).	[62]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Occludin (OCLN).	[63]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Occludin (OCLN).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Occludin (OCLN).	[65]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Occludin (OCLN).	[66]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Occludin (OCLN).	[68]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Occludin (OCLN).	[69]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Occludin (OCLN).	[59]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Occludin (OCLN).	[70]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Occludin (OCLN).	[71]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Occludin (OCLN).	[72]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Occludin (OCLN).	[73]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of Occludin (OCLN).	[74]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of Occludin (OCLN).	[62]
Lead acetate	DML0GZ2	Investigative	Lead acetate decreases the expression of Occludin (OCLN).	[75]
OXYRESVERATROL	DMN7S4L	Investigative	OXYRESVERATROL increases the expression of Occludin (OCLN).	[77]
diarylpropionitril	DM14X29	Investigative	diarylpropionitril increases the expression of Occludin (OCLN).	[78]
JWH-133	DM1DEYU	Investigative	JWH-133 increases the expression of Occludin (OCLN).	[79]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin affects the localization of Occludin (OCLN).	[44]
LY294002	DMY1AFS	Phase 1	LY294002 affects the localization of Occludin (OCLN).	[44]
PMID26560530-Compound-35	DMO36RL	Patented	PMID26560530-Compound-35 affects the localization of Occludin (OCLN).	[44]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde affects the localization of Occludin (OCLN).	[67]
PATULIN	DM0RV9C	Investigative	PATULIN increases the degradation of Occludin (OCLN).	[76]

1 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 Occludin (OCLN).	[64]

References

• [1] N-carbamylglutamate and l-arginine promote intestinal function in suckling lambs with intrauterine growth restriction by regulating antioxidant capacity via a nitric oxide-dependent pathway.Food Funct. 2019 Oct 16;10(10):6374-6384. doi: 10.1039/c9fo01752f.
• [2] Knockdown of long non-coding RNA XIST increases blood-tumor barrier permeability and inhibits glioma angiogenesis by targeting miR-137.Oncogenesis. 2017 Mar 13;6(3):e303. doi: 10.1038/oncsis.2017.7.
• [3] Vitamin A and Retinoic Acid Exhibit Protective Effects on Necrotizing Enterocolitis by Regulating Intestinal Flora and Enhancing the IntestinalEpithelial Barrier.Arch Med Res. 2018 Jan;49(1):1-9. doi: 10.1016/j.arcmed.2018.04.003. Epub 2018 Apr 24.
• [4] Acer palmatum thumb. Ethanol Extract Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation.J Immunol Res. 2018 Oct 8;2018:5718396. doi: 10.1155/2018/5718396. eCollection 2018.
• [5] The protective effect of alpha-tocopherol against dichromate-induced renal tight junction damage is mediated via ERK1/2.Toxicol Lett. 2009 Dec 15;191(2-3):279-88. doi: 10.1016/j.toxlet.2009.09.011. Epub 2009 Sep 17.
• [6] Occludin protein expression in human cervical cancer and its association with patient's clinical characteristics.J Cancer Res Ther. 2018 Jan;14(1):124-127. doi: 10.4103/jcrt.JCRT_664_17.
• [7] Selective loss of cortical endothelial tight junction proteins during Alzheimer's disease progression.Brain. 2019 Apr 1;142(4):1077-1092. doi: 10.1093/brain/awz011.
• [8] Monocytic cell junction proteins serve important roles in atherosclerosis via the endoglin pathway.Mol Med Rep. 2017 Nov;16(5):6750-6756. doi: 10.3892/mmr.2017.7444. Epub 2017 Sep 8.
• [9] Bacillus amyloliquefaciens Ameliorates H(2)O(2)-Induced Oxidative Damage by Regulating Transporters, Tight Junctions, and Apoptosis Gene Expression in Cell Line IPEC-1.Probiotics Antimicrob Proteins. 2020 Jun;12(2):649-656. doi: 10.1007/s12602-019-09538-5.
• [10] Colonization of preterm gnotobiotic piglets with probiotic Lactobacillus rhamnosus GG and its interference with Salmonella Typhimurium.Clin Exp Immunol. 2019 Mar;195(3):381-394. doi: 10.1111/cei.13236. Epub 2018 Dec 2.
• [11] Epigenetic silencing of occludin promotes tumorigenic and metastatic properties of cancer cells via modulations of unique sets of apoptosis-associated genes. Cancer Res. 2006 Sep 15;66(18):9125-33. doi: 10.1158/0008-5472.CAN-06-1864.
• [12] Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells.Oncotarget. 2018 Jul 20;9(56):30821-30836. doi: 10.18632/oncotarget.25738. eCollection 2018 Jul 20.
• [13] MCF-7 cells expressing nuclear associated lysyl oxidase-like 2 (LOXL2) exhibit an epithelial-to-mesenchymal transition (EMT) phenotype and are highly invasive in vitro. J Biol Chem. 2013 Oct 18;288(42):30000-30008. doi: 10.1074/jbc.C113.502310. Epub 2013 Sep 6.
• [14] Impairment of tight junctions and glucose transport in endothelial cells of human cerebral cavernous malformations.J Neuropathol Exp Neurol. 2011 Jun;70(6):417-29. doi: 10.1097/NEN.0b013e31821bc40e.
• [15] Downregulation of OCLN and GAS1 in clear cell renal cell carcinoma.Oncol Rep. 2017 Mar;37(3):1487-1496. doi: 10.3892/or.2017.5414. Epub 2017 Jan 31.
• [16] Incomplete cellular reprogramming of colorectal cancer cells elicits an epithelial/mesenchymal hybrid phenotype.J Biomed Sci. 2018 Jul 19;25(1):57. doi: 10.1186/s12929-018-0461-1.
• [17] Erythropoietin protects outer blood-retinal barrier in experimental diabetic retinopathy by up-regulating ZO-1 and occludin.Clin Exp Ophthalmol. 2019 Dec;47(9):1182-1197. doi: 10.1111/ceo.13619. Epub 2019 Sep 15.
• [18] Metastatic pathway-specific transcriptome analysis identifies MFSD4 as a putative tumor suppressor and biomarker for hepatic metastasis in patients with gastric cancer.Oncotarget. 2016 Mar 22;7(12):13667-79. doi: 10.18632/oncotarget.7269.
• [19] The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clin Pharmacol Ther. 2006 Oct;80(4):375-83. doi: 10.1016/j.clpt.2006.07.002.
• [20] Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma.PLoS Pathog. 2018 Mar 14;14(3):e1006916. doi: 10.1371/journal.ppat.1006916. eCollection 2018 Mar.
• [21] Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins.Am J Pathol. 2001 Dec;159(6):2001-9. doi: 10.1016/S0002-9440(10)63051-9.
• [22] Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells.Sci Rep. 2018 Oct 11;8(1):15157. doi: 10.1038/s41598-018-33566-w.
• [23] Downregulation of occludin affects the proliferation, apoptosis and metastatic properties of human lung carcinoma.Oncol Rep. 2018 Jul;40(1):454-462. doi: 10.3892/or.2018.6408. Epub 2018 May 2.
• [24] Different expression of occludin and ZO-1 in primary and metastatic liver tumors.Pathol Oncol Res. 2008 Sep;14(3):299-306. doi: 10.1007/s12253-008-9031-2. Epub 2008 Apr 2.
• [25] Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis.Mult Scler. 2010 Mar;16(3):293-302. doi: 10.1177/1352458509358189.
• [26] Defining the role of NG2-expressing cells in experimental models of multiple sclerosis. A biofunctional analysis of the neurovascular unit in wild type and NG2 null mice.PLoS One. 2019 Mar 14;14(3):e0213508. doi: 10.1371/journal.pone.0213508. eCollection 2019.
• [27] Recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria. Am J Hum Genet. 2010 Sep 10;87(3):354-64. doi: 10.1016/j.ajhg.2010.07.012. Epub 2010 Aug 19.
• [28] Opioid Receptor Agonism Preserves the Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates the Retinopathy in Experimental Diabetes.Invest Ophthalmol Vis Sci. 2019 Sep 3;60(12):3842-3853. doi: 10.1167/iovs.19-26761.
• [29] Upregulation of the Intestinal Paracellular Pathway with Breakdown of Tight and Adherens Junctions in Deficit Schizophrenia.Mol Neurobiol. 2019 Oct;56(10):7056-7073. doi: 10.1007/s12035-019-1578-2. Epub 2019 Apr 10.
• [30] Selective mGluR1 Negative Allosteric Modulator Reduces Blood-Brain Barrier Permeability and Cerebral Edema After Experimental Subarachnoid Hemorrhage.Transl Stroke Res. 2020 Aug;11(4):799-811. doi: 10.1007/s12975-019-00758-z. Epub 2019 Dec 12.
• [31] Correlation of Intestinal Mucosal Healing and Tight Junction Protein Expression in Ulcerative Colitis Patients.Am J Med Sci. 2019 Mar;357(3):195-204. doi: 10.1016/j.amjms.2018.11.011. Epub 2018 Nov 27.
• [32] Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis.Hematol Oncol. 2017 Sep;35(3):365-373. doi: 10.1002/hon.2289. Epub 2016 Mar 21.
• [33] Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival.Gastric Cancer. 2009;12(1):43-51. doi: 10.1007/s10120-008-0497-0. Epub 2009 Apr 24.
• [34] Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.PLoS One. 2013;8(2):e55116. doi: 10.1371/journal.pone.0055116. Epub 2013 Feb 4.
• [35] Dietary Fermentable Fibers Attenuate Chronic Kidney Disease in Mice by Protecting the Intestinal Barrier.J Nutr. 2018 Apr 1;148(4):552-561. doi: 10.1093/jn/nxy008.
• [36] Roseburia intestinalis inhibits oncostatin M and maintains tight junction integrity in a murine model of acute experimental colitis.Scand J Gastroenterol. 2019 Apr;54(4):432-440. doi: 10.1080/00365521.2019.1595708. Epub 2019 Apr 4.
• [37] Clinicopathologic significance of claudin-6, occludin, and matrix metalloproteinases -2 expression in ovarian carcinoma.Diagn Pathol. 2013 Nov 19;8:190. doi: 10.1186/1746-1596-8-190.
• [38] MicroRNA-126-3p/-5p Overexpression Attenuates Blood-Brain Barrier Disruption in a Mouse Model of Middle Cerebral Artery Occlusion.Stroke. 2020 Feb;51(2):619-627. doi: 10.1161/STROKEAHA.119.027531. Epub 2019 Dec 11.
• [39] Overexpression of miR-429 impairs intestinal barrier function in diabetic mice by down-regulating occludin expression.Cell Tissue Res. 2016 Nov;366(2):341-352. doi: 10.1007/s00441-016-2435-5. Epub 2016 Jun 14.
• [40] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [41] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [42] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [43] Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures. PLoS One. 2013 Dec 6;8(12):e82970. doi: 10.1371/journal.pone.0082970. eCollection 2013.
• [44] 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.
• [45] Arsenite-induced downregulation of occludin in mouse lungs and BEAS-2B cells via the ROS/ERK/ELK1/MLCK and ROS/p38 MAPK signaling pathways. Toxicol Lett. 2020 Oct 10;332:146-154. doi: 10.1016/j.toxlet.2020.07.010. Epub 2020 Jul 16.
• [46] Protective effect of quercetin on hydrogen peroxide-induced tight junction disruption. Int J Toxicol. 2010 Jul;29(4):418-24. doi: 10.1177/1091581810366487. Epub 2010 May 5.
• [47] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [48] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [49] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [50] Development of an alternative zebrafish model for drug-induced intestinal toxicity. J Appl Toxicol. 2018 Feb;38(2):259-273. doi: 10.1002/jat.3520. Epub 2017 Oct 13.
• [51] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [52] 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.
• [53] 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.
• [54] 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.
• [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] Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015 Jul;29(7):299-304. doi: 10.1002/jbt.21696. Epub 2015 Mar 9.
• [57] 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.
• [58] The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clin Pharmacol Ther. 2006 Oct;80(4):375-83. doi: 10.1016/j.clpt.2006.07.002.
• [59] Effects of glyphosate and aminomethylphosphonic acid on an isogeneic model of the human blood-brain barrier. Toxicol Lett. 2019 Apr;304:39-49. doi: 10.1016/j.toxlet.2018.12.013. Epub 2018 Dec 31.
• [60] Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact. 2010 Dec 5;188(3):659-67.
• [61] Epigenetic silencing of occludin promotes tumorigenic and metastatic properties of cancer cells via modulations of unique sets of apoptosis-associated genes. Cancer Res. 2006 Sep 15;66(18):9125-33. doi: 10.1158/0008-5472.CAN-06-1864.
• [62] The cigarette smoke components induced the cell proliferation and epithelial to mesenchymal transition via production of reactive oxygen species in endometrial adenocarcinoma cells. Food Chem Toxicol. 2018 Nov;121:657-665. doi: 10.1016/j.fct.2018.09.023. Epub 2018 Sep 17.
• [63] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [64] 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.
• [65] Regulatory and junctional proteins of the blood-testis barrier in human Sertoli cells are modified by monobutyl phthalate (MBP) and bisphenol A (BPA) exposure. Toxicol In Vitro. 2016 Aug;34:1-7. doi: 10.1016/j.tiv.2016.02.017. Epub 2016 Feb 26.
• [66] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [67] Effects of ethanol and acetaldehyde on tight junction integrity: in vitro study in a three dimensional intestinal epithelial cell culture model. PLoS One. 2012;7(4):e35008. doi: 10.1371/journal.pone.0035008. Epub 2012 Apr 19.
• [68] Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay. Toxicology. 2016 Apr 15;353-354:21-33. doi: 10.1016/j.tox.2016.05.003. Epub 2016 May 3.
• [69] Paraquat affects the differentiation of neural stem cells and impairs the function of vascular endothelial cells: a study of molecular mechanism. Environ Toxicol. 2019 Apr;34(4):548-555. doi: 10.1002/tox.22723. Epub 2019 Jan 30.
• [70] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [71] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [72] Prenatal arsenic exposure stymies gut butyrate production and enhances gut permeability in post natal life even in absence of arsenic deftly through miR122-Occludin pathway. Toxicol Lett. 2023 Feb 1;374:19-30. doi: 10.1016/j.toxlet.2022.11.011. Epub 2022 Dec 5.
• [73] 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.
• [74] Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB). Neurotoxicology. 2022 Dec;93:152-162. doi: 10.1016/j.neuro.2022.09.010. Epub 2022 Sep 24.
• [75] [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.
• [76] 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.
• [77] 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.
• [78] Oestradiol decreases colonic permeability through oestrogen receptor beta-mediated up-regulation of occludin and junctional adhesion molecule-A in epithelial cells. J Physiol. 2009 Jul 1;587(Pt 13):3317-28. doi: 10.1113/jphysiol.2009.169300. Epub 2009 May 11.
• [79] Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions. J Neurosci. 2012 Mar 21;32(12):4004-16. doi: 10.1523/JNEUROSCI.4628-11.2012.