Details of Disease

General Information of Disease (ID: DISV09JY)

• Disease Name: Keloid
• Disease Class: EE60: Keloid/hypertrophic scar
• Definition: An irregularly shaped, elevated mark on the skin caused by deposits of excessive amounts of collagen during wound healing. It extends beyond the original boundaries of the wound and may enlarge progressively.
• Disease Hierarchy:
  DISC9UKP: Reactive cutaneous fibrous lesion
  DISV09JY: Keloid
• ICD Code:
  ICD-11: ICD-11: EE60
  ICD-10: ICD-10: L73.0
  Expand ICD-11: 'EE60
  Expand ICD-10: 'L73.0
• Disease Identifiers:
  MONDO ID: MONDO_0005348
  MESH ID: D007627
  UMLS CUI: C0022548
  MedGen ID: 7197
  HPO ID: HP:0010562
  SNOMED CT ID: 33659008

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Dexamethasone	DMMWZET	Approved	Small molecular drug	[1]
Tranilast	DME5Y64	Approved	Small molecular drug	[2]
Triamcinolone	DM98IXF	Approved	Small molecular drug	[3]

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
MRG-201	DM9M5WV	Phase 2	NA	[4]
Remlarsen	DM2USXP	Phase 2	NA	[5]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 20 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
NEDD4	TT1QU6G	Limited	Biomarker	[6]
ADAM33	TTQICM2	Strong	Genetic Variation	[7]
ALB	TTFNGC9	Strong	Biomarker	[8]
APOL1	TTDB8PW	Strong	Genetic Variation	[9]
CDK11B	TT5Q79O	Strong	Genetic Variation	[10]
CLIC1	TT8KZG6	Strong	Biomarker	[8]
EIF5A	TTIVCNR	Strong	Biomarker	[8]
FGG	TTR31L7	Strong	Biomarker	[8]
FTH1	TT975ZT	Strong	Biomarker	[8]
LGALS1	TTO3NYT	Strong	Biomarker	[8]
MIF	TT6804T	Strong	Biomarker	[8]
NLRC5	TTWZC78	Strong	Biomarker	[11]
S100A12	TTQ4ESF	Strong	Altered Expression	[12]
S100A4	TTPR5SX	Strong	Biomarker	[8]
S100A8	TT4AF6N	Strong	Biomarker	[8]
S100A9	TT0TMQG	Strong	Biomarker	[8]
SERPINB5	TT1KW50	Strong	Biomarker	[8]
SERPINF1	TTR59S1	Strong	Biomarker	[8]
TAGLN	TTDRZ9H	Strong	Biomarker	[8]
SERPINH1	TTPSWQG	Definitive	Altered Expression	[13]

This Disease Is Related to 35 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
COL1A1	OTI31178	moderate	Altered Expression	[14]
HNRNPH3	OTODTW0I	moderate	Biomarker	[15]
ACTRT2	OT3Q5PQL	Strong	Biomarker	[8]
ARHGDIA	OTEXWJDO	Strong	Biomarker	[8]
ASPN	OTYJM80N	Strong	Biomarker	[16]
CAPG	OTJ86KI6	Strong	Biomarker	[8]
COL10A1	OTC4G2YC	Strong	Biomarker	[16]
COL3A1	OTT1EMLM	Strong	Biomarker	[17]
COL5A1	OT24078H	Strong	Biomarker	[8]
CRABP1	OTISDG5X	Strong	Biomarker	[8]
CTHRC1	OTV88X2G	Strong	Altered Expression	[18]
FOXL2	OTFRQUYL	Strong	Biomarker	[19]
FTL	OTYQA8A6	Strong	Biomarker	[8]
GDF9	OTNTVKVU	Strong	Biomarker	[20]
HAS1	OTJIAG1W	Strong	Biomarker	[21]
HBD	OTRQG4WA	Strong	Biomarker	[8]
HUS1B	OT3VFQWS	Strong	Genetic Variation	[22]
KLF10	OT4F4UGS	Strong	Biomarker	[23]
LAMA1	OTQZMP86	Strong	Biomarker	[21]
MMP19	OTLSTT2B	Strong	Biomarker	[24]
MYDGF	OT9HRPL6	Strong	Biomarker	[8]
MYH8	OT9F350W	Strong	Genetic Variation	[22]
MYL6B	OTWTRGT7	Strong	Biomarker	[8]
PFN1	OTHTGA1H	Strong	Biomarker	[8]
PRDX1	OTZ3BEC4	Strong	Biomarker	[8]
PRDX2	OTLWCY9T	Strong	Biomarker	[8]
RAN	OT2TER5M	Strong	Biomarker	[8]
RTTN	OT5PB986	Strong	Genetic Variation	[22]
S100A10	OTI71243	Strong	Biomarker	[8]
SERPINB2	OT72QLZB	Strong	Altered Expression	[25]
SFN	OTLJCZ1U	Strong	Biomarker	[8]
TINAGL1	OTZZO56M	Strong	Biomarker	[26]
TNFAIP6	OT1SLUZH	Strong	Biomarker	[27]
TPM1	OTD73X6R	Strong	Biomarker	[8]
TPSB2	OTN769MT	Strong	Biomarker	[8]

References

• [1] Dexamethasone FDA Label
• [2] Treatment of keloid and hypertrophic scars by iontophoretic transdermal delivery of tranilast. Scand J Plast Reconstr Surg Hand Surg. 1997 Jun;31(2):151-8.
• [3] Triamcinolone FDA Label
• [4] ClinicalTrials.gov (NCT03601052) Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids. U.S. National Institutes of Health.
• [5] ClinicalTrials.gov (NCT03601052) Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids. U.S. National Institutes of Health.
• [6] NEDD4 Is Involved in Inflammation Development during Keloid Formation.J Invest Dermatol. 2019 Feb;139(2):333-341. doi: 10.1016/j.jid.2018.07.044. Epub 2018 Sep 28.
• [7] Association of ADAM33 gene polymorphisms with keloid scars in a northeastern Chinese population.Cell Physiol Biochem. 2014;34(3):981-7. doi: 10.1159/000366314. Epub 2014 Aug 27.
• [8] Comparative proteomic analysis between normal skin and keloid scar.Br J Dermatol. 2010 Jun;162(6):1302-15. doi: 10.1111/j.1365-2133.2010.09660.x. Epub 2010 Feb 1.
• [9] Keloids and non-diabetic kidney disease: similarities and the APOL1-MYH9 haplotype as a possible genetic link.Med Hypotheses. 2013 Nov;81(5):908-10. doi: 10.1016/j.mehy.2013.08.009. Epub 2013 Aug 22.
• [10] Analyses of CDC2L1 gene mutations in keloid tissue.Clin Exp Dermatol. 2012 Apr;37(3):277-83. doi: 10.1111/j.1365-2230.2011.04225.x. Epub 2011 Dec 20.
• [11] Silencing NLRC5 inhibits extracellular matrix expression in keloid fibroblasts via inhibition of transforming growth factor-1/Smad signaling pathway.Biomed Pharmacother. 2016 Oct;83:1016-1021. doi: 10.1016/j.biopha.2016.08.012. Epub 2016 Aug 12.
• [12] S100A12 Induced in the Epidermis by Reduced Hydration Activates Dermal Fibroblasts and Causes Dermal Fibrosis.J Invest Dermatol. 2017 Mar;137(3):650-659. doi: 10.1016/j.jid.2016.10.040. Epub 2016 Nov 10.
• [13] Detection of substrate binding of a collagen-specific molecular chaperone HSP47 in solution using fluorescence correlation spectroscopy.Biochem Biophys Res Commun. 2018 Feb 26;497(1):279-284. doi: 10.1016/j.bbrc.2018.02.069. Epub 2018 Feb 10.
• [14] miR-96 promotes collagen deposition in keloids by targeting Smad7.Exp Ther Med. 2019 Jan;17(1):773-781. doi: 10.3892/etm.2018.7008. Epub 2018 Nov 23.
• [15] Tacrolimus fails to regulate collagen expression in dermal fibroblasts.J Surg Res. 2013 Sep;184(1):678-90. doi: 10.1016/j.jss.2013.04.006. Epub 2013 Apr 25.
• [16] Aberrant connective tissue differentiation towards cartilage and bone underlies human keloids in African Americans.Exp Dermatol. 2017 Aug;26(8):721-727. doi: 10.1111/exd.13271. Epub 2017 Feb 28.
• [17] miR-21 promotes collagen production in keloid via Smad7.Burns. 2017 May;43(3):555-561. doi: 10.1016/j.burns.2016.09.013. Epub 2016 Oct 4.
• [18] Increased Cthrc1 Activates Normal Fibroblasts and Suppresses Keloid Fibroblasts by Inhibiting TGF-/Smad Signal Pathway and Modulating YAP Subcellular Location.Curr Med Sci. 2018 Oct;38(5):894-902. doi: 10.1007/s11596-018-1959-1. Epub 2018 Oct 20.
• [19] A genome-wide association study identifies four susceptibility loci for keloid in the Japanese population.Nat Genet. 2010 Sep;42(9):768-71. doi: 10.1038/ng.645. Epub 2010 Aug 15.
• [20] Growth Differentiation Factor-9 Promotes Fibroblast Proliferation and Migration in Keloids through the Smad2/3 Pathway.Cell Physiol Biochem. 2016;40(1-2):207-218. doi: 10.1159/000452538. Epub 2016 Nov 18.
• [21] Characterization of In Vitro Reconstructed Human Normotrophic, Hypertrophic, and Keloid Scar Models.Tissue Eng Part C Methods. 2018 Apr;24(4):242-253. doi: 10.1089/ten.TEC.2017.0464. Epub 2018 Apr 2.
• [22] Differential susceptible loci expression in keloid and hypertrophic scars in the Chinese Han population.Ann Plast Surg. 2015 Jan;74(1):26-9. doi: 10.1097/SAP.0000000000000364.
• [23] TIEG1 Represses Smad7-Mediated Activation of TGF-1/Smad Signaling inKeloid Pathogenesis.J Invest Dermatol. 2017 May;137(5):1051-1059. doi: 10.1016/j.jid.2016.12.019. Epub 2017 Jan 17.
• [24] Identification of biomarkers involved in differential profiling of hypertrophic and keloid scars versus normal skin.Arch Dermatol Res. 2015 Mar;307(2):115-33. doi: 10.1007/s00403-014-1512-4. Epub 2014 Oct 17.
• [25] Association of plasminogen activator inhibitor-1 and vitamin D receptor expression with the risk of keloid disease in a Chinese population.Kaohsiung J Med Sci. 2017 Jan;33(1):24-29. doi: 10.1016/j.kjms.2016.10.013. Epub 2016 Dec 9.
• [26] High in situ mRNA levels of IL-22, TFG-, and ARG-1 in keloid scars.Immunobiology. 2018 Dec;223(12):812-817. doi: 10.1016/j.imbio.2018.08.010. Epub 2018 Aug 20.
• [27] Invitro analysis of the role of tumor necrosis factorstimulated gene? in keloid.Mol Med Rep. 2019 Feb;19(2):919-926. doi: 10.3892/mmr.2018.9767. Epub 2018 Dec 14.