Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW5Z1NH)

• DOT Name: Resistin (RETN)
• Synonyms: Adipose tissue-specific secretory factor; ADSF; C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein; Cysteine-rich secreted protein A12-alpha-like 2; Cysteine-rich secreted protein FIZZ3
• Gene Name: RETN
• Related Disease:
  End-stage renal disease
  Endometrial cancer
  Endometrial carcinoma
  Alzheimer disease
  Anorexia nervosa cachexia
  Atrial fibrillation
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Chronic renal failure
  Clear cell renal carcinoma
  Colitis
  Congestive heart failure
  Coronary atherosclerosis
  Crohn disease
  Endometriosis
  Epithelial ovarian cancer
  Fatty liver disease
  Hepatitis
  Hepatitis C virus infection
  Heroin dependence
  High blood pressure
  Liver cirrhosis
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metabolic disorder
  Osteoarthritis
  Peripheral arterial disease
  Psoriasis
  Renal cell carcinoma
  Stroke
  Systemic lupus erythematosus
  Systemic sclerosis
  Vitamin D deficiency
  Coronary heart disease
  Hyperinsulinemia
  Myocardial infarction
  Neoplasm
  Non-alcoholic fatty liver disease
  Arthritis
  Inflammatory bowel disease
  Knee osteoarthritis
  Nephropathy
  Obsolete diabetes mellitus, noninsulin-dependent
  Osteoporosis
  Plasma cell myeloma
• UniProt ID: RETN_HUMAN
• Pfam ID: PF06954
• Sequence:
  MKALCLLLLPVLGLLVSSKTLCSMEEAINERIQEVAGSLIFRAISSIGLECQSVTSRGDL
  ATCPRGFAVTGCTCGSACGSWDVRAETTCHCQCAGMDWTGARCCRVQP
• Function: Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells. Potentially links obesity to diabetes. Promotes chemotaxis in myeloid cells.
• Tissue Specificity: Expressed in white adipose tissue (at protein level) . Widely expressed, with particularly strong expression in lung, bone marrow, breast and peripheral blood . Expressed strongly in bone marrow and at lower levels in lung, but not detected in other tissues . Isoform 2 is detected in adipose tissue, bone marrow, brain, lung, peripheral blood, placenta and thymus .
• Reactome Pathway:
  FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes (R-HSA-9615017)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
End-stage renal disease	DISXA7GG	Definitive	Altered Expression	[1]
Endometrial cancer	DISW0LMR	Definitive	Genetic Variation	[2]
Endometrial carcinoma	DISXR5CY	Definitive	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Biomarker	[4]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Cardiac failure	DISDC067	Strong	Altered Expression	[7]
Chronic renal failure	DISGG7K6	Strong	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Colitis	DISAF7DD	Strong	Altered Expression	[9]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[7]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[10]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[11]
Endometriosis	DISX1AG8	Strong	Altered Expression	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[13]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[14]
Hepatitis	DISXXX35	Strong	Altered Expression	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[16]
Heroin dependence	DISQ1H57	Strong	Biomarker	[17]
High blood pressure	DISY2OHH	Strong	Biomarker	[18]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[19]
Lung cancer	DISCM4YA	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[20]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[21]
Peripheral arterial disease	DIS78WFB	Strong	Altered Expression	[22]
Psoriasis	DIS59VMN	Strong	Altered Expression	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[8]
Stroke	DISX6UHX	Strong	Biomarker	[24]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[25]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[26]
Vitamin D deficiency	DISAWKYI	Strong	Biomarker	[27]
Coronary heart disease	DIS5OIP1	moderate	Biomarker	[28]
Hyperinsulinemia	DISIDWT6	moderate	Biomarker	[29]
Myocardial infarction	DIS655KI	moderate	Altered Expression	[30]
Neoplasm	DISZKGEW	moderate	Altered Expression	[31]
Non-alcoholic fatty liver disease	DISDG1NL	moderate	Altered Expression	[32]
Arthritis	DIST1YEL	Limited	Altered Expression	[33]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[34]
Knee osteoarthritis	DISLSNBJ	Limited	Genetic Variation	[35]
Nephropathy	DISXWP4P	Limited	Biomarker	[36]
Obsolete diabetes mellitus, noninsulin-dependent	DISS46MZ	Limited	Autosomal dominant	[37]
Osteoporosis	DISF2JE0	Limited	Biomarker	[38]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[39]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
D-glucose	DMMG2TO	Investigative	Resistin (RETN) decreases the uptake of D-glucose.	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Resistin (RETN).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Resistin (RETN).	[41]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Resistin (RETN).	[42]
Hesperetin	DMKER83	Approved	Hesperetin decreases the expression of Resistin (RETN).	[43]
Vitamin B3	DMQVRZH	Approved	Vitamin B3 decreases the expression of Resistin (RETN).	[44]
Amlodipine	DMBDAZV	Approved	Amlodipine decreases the expression of Resistin (RETN).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Resistin (RETN).	[47]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Resistin (RETN).	[48]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Resistin (RETN).	[49]
Icosapentum	DMF1CM7	Investigative	Icosapentum decreases the expression of Resistin (RETN).	[49]
isobutylmethylxanthine	DM46F5X	Investigative	isobutylmethylxanthine increases the expression of Resistin (RETN).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Resistin (RETN).	[46]

References

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• [2] Investigation of resistin 420 and 62 gene polymorphism in patients with endometrial cancer.Taiwan J Obstet Gynecol. 2019 Jan;58(1):164-167. doi: 10.1016/j.tjog.2018.11.030.
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• [10] Resistin promotes cardiac homing of mesenchymal stem cells and functional recovery after myocardial ischemia-reperfusion via the ERK1/2-MMP-9 pathway.Am J Physiol Heart Circ Physiol. 2019 Jan 1;316(1):H233-H244. doi: 10.1152/ajpheart.00457.2018. Epub 2018 Nov 9.
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• [16] Circulating Resistin Is Associated with Plasma Glucagon-Like Peptide-1 in Cirrhotic Patients with Hepatitis C Virus Genotype-4 Infection.Endocr Res. 2020 Feb;45(1):17-23. doi: 10.1080/07435800.2019.1627551. Epub 2019 Jun 10.
• [17] Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment. Physiol Res. 2005;54(1):73-78. doi: 10.33549/physiolres.930568.
• [18] Resistin Mediates Sex-Dependent Effects of Perivascular Adipose Tissue on Vascular Function in the Shrsp.Sci Rep. 2019 May 3;9(1):6897. doi: 10.1038/s41598-019-43326-z.
• [19] Increased resistin suggests poor prognosis and promotes development of lung adenocarcinoma.Oncol Rep. 2018 Dec;40(6):3392-3404. doi: 10.3892/or.2018.6736. Epub 2018 Sep 26.
• [20] Adipose tissue dysfunction and metabolic disorders: Is it possible to predict who will develop type 2 diabetes mellitus? Role of markErs in the progreSsion of dIabeteS in obese paTIeNts (The RESISTIN trial).Cytokine. 2020 Mar;127:154947. doi: 10.1016/j.cyto.2019.154947. Epub 2019 Dec 4.
• [21] Resistin Enhances Monocyte Chemoattractant Protein-1 Production in Human Synovial Fibroblasts and Facilitates Monocyte Migration.Cell Physiol Biochem. 2019;52(3):408-420. doi: 10.33594/000000029. Epub 2019 Mar 8.
• [22] Leptinemia is Associated With Peripheral ArteryDisease.J Surg Res. 2019 Jun;238:48-56. doi: 10.1016/j.jss.2019.01.023. Epub 2019 Feb 6.
• [23] Biomarkers of Inflammation in Obesity-Psoriatic Patients.Mediators Inflamm. 2019 May 28;2019:7353420. doi: 10.1155/2019/7353420. eCollection 2019.
• [24] Selected adipose tissue hormones in the blood of patients with ischaemic cerebral stroke.Endokrynol Pol. 2020;71(1):21-26. doi: 10.5603/EP.a2019.0057. Epub 2019 Dec 18.
• [25] Adipokine interactions promote the pathogenesis of systemic lupus erythematosus.Cytokine. 2018 Nov;111:20-27. doi: 10.1016/j.cyto.2018.08.002. Epub 2018 Aug 8.
• [26] Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement.Cytokine. 2019 May;117:41-49. doi: 10.1016/j.cyto.2018.11.013. Epub 2019 Feb 19.
• [27] Vitamin D Insufficiency in Overweight and Obese Children and Adolescents.Front Endocrinol (Lausanne). 2019 Mar 1;10:103. doi: 10.3389/fendo.2019.00103. eCollection 2019.
• [28] Implications of resistin in type 2 diabetes mellitus and coronary artery disease: Impairing insulin function and inducing pro-inflammatory cytokines.J Cell Physiol. 2019 Dec;234(12):21758-21769. doi: 10.1002/jcp.28913. Epub 2019 Jun 11.
• [29] Celastrol attenuates adipokine resistin-associated matrix interaction and migration of vascular smooth muscle cells.J Cell Biochem. 2013 Feb;114(2):398-408. doi: 10.1002/jcb.24374.
• [30] Plasma adiponectin and resistin levels as predictors of mortality in patients with acute myocardial infarction: data from infarction prognosis study registry.Coron Artery Dis. 2009 Jan;20(1):33-9. doi: 10.1097/MCA.0b013e328318ecb0.
• [31] Resistin effects on pancreatic cancer progression and chemoresistance are mediated through its receptors CAP1 and TLR4.J Cell Physiol. 2019 Jun;234(6):9457-9466. doi: 10.1002/jcp.27631. Epub 2018 Oct 14.
• [32] MiR-34a regulates mitochondrial content and fat ectopic deposition induced by resistin through the AMPK/PPAR pathway in HepG2 cells.Int J Biochem Cell Biol. 2018 Jan;94:133-145. doi: 10.1016/j.biocel.2017.11.008. Epub 2017 Nov 29.
• [33] Resistin Promotes Angiogenesis in Endothelial Progenitor Cells Through Inhibition of MicroRNA206: Potential Implications for Rheumatoid Arthritis.Stem Cells. 2015 Jul;33(7):2243-55. doi: 10.1002/stem.2024. Epub 2015 May 13.
• [34] Association Between Adipokines Levels with Inflammatory Bowel Disease (IBD): Systematic Reviews.Dig Dis Sci. 2017 Dec;62(12):3280-3286. doi: 10.1007/s10620-017-4806-5. Epub 2017 Oct 30.
• [35] Role of resistin genetic variations in knee osteoarthritis pathogenesis, a cross sectional study.Mol Biol Rep. 2019 Jun;46(3):2657-2663. doi: 10.1007/s11033-019-04673-2. Epub 2019 Mar 22.
• [36] Resistin as a potential marker of renal disease in lupus nephritis.Clin Exp Immunol. 2015 Mar;179(3):435-43. doi: 10.1111/cei.12473.
• [37] 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.
• [38] Assessment of selected adipocytokines in obese women with postmenopausal osteoporosis.Endokrynol Pol. 2019;70(6):478-483. doi: 10.5603/EP.a2019.0043. Epub 2019 Sep 30.
• [39] Resistin induces multidrug resistance in myeloma by inhibiting cell death and upregulating ABC transporter expression.Haematologica. 2017 Jul;102(7):1273-1280. doi: 10.3324/haematol.2016.154062. Epub 2017 Mar 30.
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• [41] PML-RAR interaction with TRIB3 impedes PPAR/RXR function and triggers dyslipidemia in acute promyelocytic leukemia. Theranostics. 2020 Aug 15;10(22):10326-10340. doi: 10.7150/thno.45924. eCollection 2020.
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• [43] Hesperetin inhibit adipocyte differentiation and enhance Bax- and p21-mediated adipolysis in human mesenchymal stem cell adipogenesis. J Biochem Mol Toxicol. 2015 Mar;29(3):99-108. doi: 10.1002/jbt.21672. Epub 2014 Oct 26.
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• [45] Amlodipine improves endothelial function and metabolic parameters in patients with hypertension. Int J Cardiol. 2009 Mar 20;133(1):23-31. doi: 10.1016/j.ijcard.2007.11.058. Epub 2008 Jan 15.
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• [47] Bisphenol A is associated with insulin resistance and modulates adiponectin and resistin gene expression in obese children. Pediatr Obes. 2017 Oct;12(5):380-387. doi: 10.1111/ijpo.12154. Epub 2016 May 17.
• [48] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [49] Fatty acids and expression of adipokines. Biochim Biophys Acta. 2005 May 30;1740(2):287-92. doi: 10.1016/j.bbadis.2004.11.019. Epub 2004 Dec 8.
• [50] Aloe-emodin inhibits adipocyte differentiation and maturation during in vitro human mesenchymal stem cell adipogenesis. J Biochem Mol Toxicol. 2012 Aug;26(8):291-300. doi: 10.1002/jbt.21415. Epub 2012 May 29.
• [51] Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab. 2003 Dec;88(12):6098-106. doi: 10.1210/jc.2003-030898.