Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO2BC0F)

• DOT Name: Transcription factor GATA-6 (GATA6)
• Synonyms: GATA-binding factor 6
• Gene Name: GATA6
• Related Disease:
  Atrial septal defect 9
  Atrioventricular septal defect 5
  GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes
  Glioblastoma multiforme
  Pancreatic hypoplasia-diabetes-congenital heart disease syndrome
  Adrenocortical carcinoma
  Atrial fibrillation
  Atrial septal defect
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Cholangiocarcinoma
  Colon cancer
  Colorectal carcinoma
  Congenital contractural arachnodactyly
  Congenital heart disease
  Epithelial ovarian cancer
  Gastric cancer
  Hyperglycemia
  Lung carcinoma
  Lung neoplasm
  Neonatal diabetes mellitus
  Neoplasm
  Obsolete metabolic syndrome
  Ovarian cancer
  Pancreatic ductal carcinoma
  Polydactyly
  Pulmonary hypertension
  Stomach cancer
  Type-1/2 diabetes
  Ventricular septal defect
  Carcinoma
  Lung adenocarcinoma
  Lung squamous cell carcinoma
  Tetralogy of fallot
  Familial atrial fibrillation
  Non-insulin dependent diabetes
  Colon carcinoma
  Congenital diaphragmatic hernia
  Conotruncal heart malformations
  Endometriosis
  Germ cell tumor
  Hepatocellular carcinoma
  Lung cancer
  Monogenic diabetes
  Non-small-cell lung cancer
  Pancreatic cancer
  Patent ductus arteriosus
  Persistent truncus arteriosus
• UniProt ID: GATA6_HUMAN
• Pfam ID: PF00320 ; PF05349
• Sequence:
  MALTDGGWCLPKRFGAAGADASDSRAFPAREPSTPPSPISSSSSSCSRGGERGPGGASNC
  GTPQLDTEAAAGPPARSLLLSSYASHPFGAPHGPSAPGVAGPGGNLSSWEDLLLFTDLDQ
  AATASKLLWSSRGAKLSPFAPEQPEEMYQTLAALSSQGPAAYDGAPGGFVHSAAAAAAAA
  AAASSPVYVPTTRVGSMLPGLPYHLQGSGSGPANHAGGAGAHPGWPQASADSPPYGSGGG
  AAGGGAAGPGGAGSAAAHVSARFPYSPSPPMANGAAREPGGYAAAGSGGAGGVSGGGSSL
  AAMGGREPQYSSLSAARPLNGTYHHHHHHHHHHPSPYSPYVGAPLTPAWPAGPFETPVLH
  SLQSRAGAPLPVPRGPSADLLEDLSESRECVNCGSIQTPLWRRDGTGHYLCNACGLYSKM
  NGLSRPLIKPQKRVPSSRRLGLSCANCHTTTTTLWRRNAEGEPVCNACGLYMKLHGVPRP
  LAMKKEGIQTRKRKPKNINKSKTCSGNSNNSIPMTPTSTSSNSDDCSKNTSPTTQPTASG
  AGAPVMTGAGESTNPENSELKYSGQDGLYIGVSLASPAEVTSSVRPDSWCALALA
• Function: Transcriptional activator. Regulates SEMA3C and PLXNA2. Involved in gene regulation specifically in the gastric epithelium. May regulate genes that protect epithelial cells from bacterial infection. Involved in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions. In human skin, controls several physiological processes contributing to homeostasis of the upper pilosebaceous unit. Triggers ductal and sebaceous differentiation as well as limits cell proliferation and lipid production to prevent hyperseborrhoea. Mediates the effects of retinoic acid on sebocyte proliferation, differentiation and lipid production. Also contributes to immune regulation of sebocytes and antimicrobial responses by modulating the expression of anti-inflammatory genes such as IL10 and pro-inflammatory genes such as IL6, TLR2, TLR4, and IFNG. Activates TGFB1 signaling which controls the interfollicular epidermis fate.
• Tissue Specificity: Expressed in heart, gut and gut-derived tissues. Expressed in skin upper pilosebaceous unit. Expression is decreased or lost in acne lesions .
• Reactome Pathway:
  Cardiogenesis (R-HSA-9733709)
  Formation of definitive endoderm (R-HSA-9823730)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  Surfactant metabolism (R-HSA-5683826)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial septal defect 9	DIS6XRGG	Definitive	Autosomal dominant	[1]
Atrioventricular septal defect 5	DISDU9K4	Definitive	Autosomal dominant	[2]
GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes	DISZB39O	Definitive	Autosomal dominant	[3]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[4]
Pancreatic hypoplasia-diabetes-congenital heart disease syndrome	DISR6WPA	Definitive	Autosomal dominant	[5]
Adrenocortical carcinoma	DISZF4HX	Strong	Biomarker	[6]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[7]
Atrial septal defect	DISJT76B	Strong	CausalMutation	[8]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[9]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[10]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[11]
Colon cancer	DISVC52G	Strong	Altered Expression	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[13]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[11]
Congenital heart disease	DISQBA23	Strong	Genetic Variation	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[15]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[16]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[17]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[15]
Lung neoplasm	DISVARNB	Strong	Biomarker	[18]
Neonatal diabetes mellitus	DISFHF9K	Strong	Autosomal dominant	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Obsolete metabolic syndrome	DISH33EG	Strong	Autosomal dominant	[19]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[15]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Biomarker	[21]
Polydactyly	DIS25BMZ	Strong	Posttranslational Modification	[22]
Pulmonary hypertension	DIS1RSP5	Strong	Biomarker	[23]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[16]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[24]
Ventricular septal defect	DISICO41	Strong	Genetic Variation	[25]
Carcinoma	DISH9F1N	moderate	Altered Expression	[26]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[27]
Lung squamous cell carcinoma	DISXPIBD	moderate	Biomarker	[28]
Tetralogy of fallot	DISMHFNW	Moderate	Autosomal dominant	[29]
Familial atrial fibrillation	DISL4AGF	Supportive	Autosomal dominant	[30]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[31]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[12]
Congenital diaphragmatic hernia	DIS0IPVU	Limited	Genetic Variation	[32]
Conotruncal heart malformations	DIS7FMIG	Limited	Autosomal recessive	[29]
Endometriosis	DISX1AG8	Limited	Biomarker	[33]
Germ cell tumor	DIS62070	Limited	Biomarker	[34]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[20]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[15]
Monogenic diabetes	DISEB8Q0	Limited	Biomarker	[35]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[36]
Pancreatic cancer	DISJC981	Limited	Biomarker	[21]
Patent ductus arteriosus	DIS9P8YS	Limited	CausalMutation	[8]
Persistent truncus arteriosus	DISRZ8EA	Limited	Genetic Variation	[37]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Warfarin	DMJYCVW	Approved	Transcription factor GATA-6 (GATA6) affects the response to substance of Warfarin.	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Transcription factor GATA-6 (GATA6).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor GATA-6 (GATA6).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor GATA-6 (GATA6).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor GATA-6 (GATA6).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor GATA-6 (GATA6).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription factor GATA-6 (GATA6).	[43]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription factor GATA-6 (GATA6).	[39]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor GATA-6 (GATA6).	[44]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription factor GATA-6 (GATA6).	[45]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Transcription factor GATA-6 (GATA6).	[46]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transcription factor GATA-6 (GATA6).	[47]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Transcription factor GATA-6 (GATA6).	[48]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Transcription factor GATA-6 (GATA6).	[40]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Transcription factor GATA-6 (GATA6).	[40]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Transcription factor GATA-6 (GATA6).	[40]
EXISULIND	DMBY56U	Phase 3	EXISULIND decreases the expression of Transcription factor GATA-6 (GATA6).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor GATA-6 (GATA6).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription factor GATA-6 (GATA6).	[50]
CHIR-99021	DMB8MNU	Patented	CHIR-99021 increases the expression of Transcription factor GATA-6 (GATA6).	[51]
NS398	DMINUWH	Terminated	NS398 decreases the expression of Transcription factor GATA-6 (GATA6).	[49]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription factor GATA-6 (GATA6).	[52]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Transcription factor GATA-6 (GATA6).	[53]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Transcription factor GATA-6 (GATA6).	[39]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Transcription factor GATA-6 (GATA6).	[40]

References

• [1] A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect. J Hum Genet. 2010 Oct;55(10):662-7. doi: 10.1038/jhg.2010.84. Epub 2010 Jul 15.
• [2] Identification of GATA6 sequence variants in patients with congenital heart defects. Pediatr Res. 2010 Oct;68(4):281-5. doi: 10.1203/PDR.0b013e3181ed17e4.
• [3] 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.
• [4] The promoter hypermethylation status of GATA6, MGMT, and FHIT in glioblastoma.Cell Mol Neurobiol. 2012 Mar;32(2):237-44. doi: 10.1007/s10571-011-9753-7. Epub 2011 Sep 18.
• [5] GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat Genet. 2011 Dec 11;44(1):20-22. doi: 10.1038/ng.1035.
• [6] Transcription factors GATA-6, SF-1, and cell proliferation in human adrenocortical tumors.Mol Cell Endocrinol. 2005 Apr 15;233(1-2):47-56. doi: 10.1016/j.mce.2005.01.012.
• [7] Gain-of-function mutations in GATA6 lead to atrial fibrillation.Heart Rhythm. 2017 Feb;14(2):284-291. doi: 10.1016/j.hrthm.2016.10.014. Epub 2016 Oct 15.
• [8] Whole exome sequencing identifies de novo mutations in GATA6 associated with congenital diaphragmatic hernia.J Med Genet. 2014 Mar;51(3):197-202. doi: 10.1136/jmedgenet-2013-101989. Epub 2014 Jan 2.
• [9] GATA-6 and NF-B activate CPI-17 gene transcription and regulate Ca2+ sensitization of smooth muscle contraction.Mol Cell Biol. 2013 Mar;33(5):1085-102. doi: 10.1128/MCB.00626-12. Epub 2012 Dec 28.
• [10] GATA5 activation of the progesterone receptor gene promoter in breast cancer cells is influenced by the +331G/A polymorphism.Cancer Res. 2006 Feb 1;66(3):1384-90. doi: 10.1158/0008-5472.CAN-05-2715.
• [11] The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma.Int J Oncol. 2019 Sep;55(3):657-670. doi: 10.3892/ijo.2019.4837. Epub 2019 Jul 15.
• [12] The miR-196b miRNA inhibits the GATA6 intestinal transcription factor and is upregulated in colon cancer patients.Oncotarget. 2017 Jan 17;8(3):4747-4759. doi: 10.18632/oncotarget.13580.
• [13] miR-455 Functions as a Tumor Suppressor Through Targeting GATA6 in Colorectal Cancer.Oncol Res. 2019 Feb 21;27(3):311-316. doi: 10.3727/096504018X15220579006875. Epub 2018 Apr 3.
• [14] Targeted sequencing identifies novel GATA6 variants in a large cohort of patients with conotruncal heart defects.Gene. 2018 Jan 30;641:341-348. doi: 10.1016/j.gene.2017.10.083. Epub 2017 Oct 31.
• [15] Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers.Clin Genet. 2020 Jan;97(1):64-72. doi: 10.1111/cge.13630. Epub 2019 Aug 28.
• [16] GATA6 suppresses migration and metastasis by regulating the miR-520b/CREB1 axis in gastric cancer.Cell Death Dis. 2019 Jan 15;10(2):35. doi: 10.1038/s41419-018-1270-x.
• [17] Negative impact of hyperglycaemia on mouse alveolar development.Cell Cycle. 2018;17(1):80-91. doi: 10.1080/15384101.2017.1403683. Epub 2017 Dec 21.
• [18] Codon 12 region of mouse K-ras gene is the site for in vitro binding of transcription factors GATA-6 and NF-Y.Biochemistry (Mosc). 2005 Oct;70(10):1180-4. doi: 10.1007/s10541-005-0244-7.
• [19] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [20] Deregulated GATA6 modulates stem cell-like properties and metabolic phenotype in hepatocellular carcinoma.Int J Cancer. 2019 Oct 1;145(7):1860-1873. doi: 10.1002/ijc.32248. Epub 2019 Mar 28.
• [21] GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer.Gut. 2017 Sep;66(9):1665-1676. doi: 10.1136/gutjnl-2015-311256. Epub 2016 Jun 20.
• [22] Gata6 restricts Isl1 to the posterior of nascent hindlimb buds through Isl1 cis-regulatory modules.Dev Biol. 2018 Feb 1;434(1):74-83. doi: 10.1016/j.ydbio.2017.11.013. Epub 2017 Dec 7.
• [23] Simvastatin restores down-regulated GATA-6 expression in pulmonary hypertensive rats.Exp Lung Res. 2009 Jun;35(5):411-26. doi: 10.1080/01902140902736819.
• [24] Case report: maternal mosaicism resulting in inheritance of a novel GATA6 mutation causing pancreatic agenesis and neonatal diabetes mellitus.Diagn Pathol. 2017 Jan 3;12(1):1. doi: 10.1186/s13000-016-0592-1.
• [25] Novel and functional DNA sequence variants within the GATA6 gene promoter in ventricular septal defects.Int J Mol Sci. 2014 Jul 17;15(7):12677-87. doi: 10.3390/ijms150712677.
• [26] Frequent genomic copy number gain and overexpression of GATA-6 in pancreatic carcinoma.Cancer Biol Ther. 2008 Oct;7(10):1593-601. doi: 10.4161/cbt.7.10.6565. Epub 2008 Oct 7.
• [27] GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, hepatocyte nuclear factor 4 expression, and KRAS mutations.Histopathology. 2018 Jul;73(1):38-48. doi: 10.1111/his.13500. Epub 2018 Apr 17.
• [28] SFTA1P, LINC00968, GATA6-AS1, TBX5-AS1, and FEZF1-AS1 are crucial long non-coding RNAs associated with the prognosis of lung squamous cell carcinoma.Oncol Lett. 2019 Oct;18(4):3985-3993. doi: 10.3892/ol.2019.10744. Epub 2019 Aug 14.
• [29] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [30] Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation. Int J Mol Med. 2012 Oct;30(4):783-90. doi: 10.3892/ijmm.2012.1068. Epub 2012 Jul 18.
• [31] Pancreatic Histopathology of Human Monogenic Diabetes Due to Causal Variants in KCNJ11, HNF1A, GATA6, and LMNA.J Clin Endocrinol Metab. 2018 Jan 1;103(1):35-45. doi: 10.1210/jc.2017-01159.
• [32] A novel GATA6 variant in a boy with neonatal diabetes and diaphragmatic hernia: a familial case with a review of the literature.J Pediatr Endocrinol Metab. 2019 Sep 25;32(9):1027-1030. doi: 10.1515/jpem-2019-0057.
• [33] The Essential Role of GATA6 in the Activation of Estrogen Synthesis in Endometriosis.Reprod Sci. 2019 Jan;26(1):60-69. doi: 10.1177/1933719118756751. Epub 2018 Feb 5.
• [34] Transcription factors GATA-4 and GATA-6, and their potential downstream effectors in ovarian germ cell tumors.Tumour Biol. 2005 Sep-Oct;26(5):265-73. doi: 10.1159/000087565. Epub 2005 Aug 17.
• [35] Two novel GATA6 mutations cause childhood-onset diabetes mellitus, pancreas malformation and congenital heart disease.Horm Res Paediatr. 2013;79(4):250-6. doi: 10.1159/000348844. Epub 2013 Apr 26.
• [36] GATA6-upregulating autophagy promotes TKI resistance in nonsmall cell lung cancer.Cancer Biol Ther. 2019;20(9):1206-1212. doi: 10.1080/15384047.2019.1599665. Epub 2019 May 16.
• [37] A novel mutation in GATA6 causes pancreatic agenesis.Pediatr Diabetes. 2015 Feb;16(1):67-70. doi: 10.1111/pedi.12111. Epub 2014 Jan 17.
• [38] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [39] 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.
• [40] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [41] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [42] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [43] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [44] 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.
• [45] 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.
• [46] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [47] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [48] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [49] GATA-6 transcriptional regulation of 15-lipoxygenase-1 during NSAID-induced apoptosis in colorectal cancer cells. Cancer Res. 2002 Feb 15;62(4):1178-83.
• [50] 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.
• [51] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [52] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [53] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [54] Genetic variations in the transcription factors GATA4 and GATA6 and bleeding complications in patients receiving warfarin therapy. Drug Des Devel Ther. 2019 May 17;13:1717-1727. doi: 10.2147/DDDT.S198018. eCollection 2019.