Growth factor

Protein or other substance that stimulates cellular proliferation

"Growth factors" redirects here. For the journal, see Growth Factors (journal).

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A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation.[1] Usually it is a secreted protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes.

Growth factors typically act as signaling molecules between cells. Examples are cytokines and hormones that bind to specific receptors on the surface of their target cells.

They often promote cell differentiation and maturation, which varies between growth factors. For example, epidermal growth factor (EGF) enhances osteogenic differentiation (osteogenesis or bone formation),[2] while fibroblast growth factors and vascular endothelial growth factors stimulate blood vessel differentiation (angiogenesis).

## Comparison to cytokines

[edit]

Growth factor is sometimes used interchangeably among scientists with the term cytokine.[3] Historically, cytokines were associated with hematopoietic (blood and lymph forming) cells and immune system cells (e.g., lymphocytes and tissue cells from spleen, thymus, and lymph nodes). For the circulatory system and bone marrow in which cells can occur in a liquid suspension and not bound up in solid tissue, it makes sense for them to communicate by soluble, circulating protein molecules. However, as different lines of research converged, it became clear that some of the same signaling proteins which the hematopoietic and immune systems use were also being used by all sorts of other cells and tissues, during development and in the mature organism.

While growth factor implies a positive effect on cell proliferation, cytokine is a neutral term with respect to whether a molecule affects proliferation. While some cytokines can be growth factors, such as G-CSF and GM-CSF, others have an inhibitory effect on cell growth or cell proliferation. Some cytokines, such as Fas ligand, are used as "death" signals; they cause target cells to undergo programmed cell death or apoptosis.

The nerve growth factor (NGF) was first discovered by Rita Levi-Montalcini, which won her a Nobel Prize in Physiology or Medicine.

## List of classes

[edit]

This list is incomplete; you can help by adding missing items. (February 2011)

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Individual growth factor proteins tend to occur as members of larger families of structurally and evolutionarily related proteins. There are many families, some of which are listed below:

* Adrenomedullin (AM)
* Angiopoietin (Ang)
* Autocrine motility factor
* Bone morphogenetic proteins (BMPs)
* Ciliary neurotrophic factor family
* Ciliary neurotrophic factor (CNTF)
* Leukemia inhibitory factor (LIF)
* Interleukin-6 (IL-6)
* Colony-stimulating factors
* Macrophage colony-stimulating factor (M-CSF)
* Granulocyte colony-stimulating factor (G-CSF)
* Granulocyte macrophage colony-stimulating factor (GM-CSF)
* Epidermal growth factor (EGF)
* Ephrins
* Ephrin A1
* Ephrin A2
* Ephrin A3
* Ephrin A4
* Ephrin A5
* Ephrin B1
* Ephrin B2
* Ephrin B3
* Erythropoietin (EPO)
* Fibroblast growth factor (FGF)
* Fibroblast growth factor 1(FGF1)
* Fibroblast growth factor 2(FGF2)
* Fibroblast growth factor 3(FGF3)
* Fibroblast growth factor 4(FGF4)
* Fibroblast growth factor 5(FGF5)
* Fibroblast growth factor 6(FGF6)
* Fibroblast growth factor 7(FGF7)
* Fibroblast growth factor 8(FGF8)
* Fibroblast growth factor 9(FGF9)
* Fibroblast growth factor 10(FGF10)
* Fibroblast growth factor 11(FGF11)
* Fibroblast growth factor 12(FGF12)
* Fibroblast growth factor 13(FGF13)
* Fibroblast growth factor 14(FGF14)
* Fibroblast growth factor 15(FGF15)
* Fibroblast growth factor 16(FGF16)
* Fibroblast growth factor 17(FGF17)
* Fibroblast growth factor 18(FGF18)
* Fibroblast growth factor 19(FGF19)
* Fibroblast growth factor 20(FGF20)
* Fibroblast growth factor 21(FGF21)
* Fibroblast growth factor 22(FGF22)
* Fibroblast growth factor 23(FGF23)
* Foetal Bovine Somatotrophin (FBS)
* GDNF family of ligands
* Glial cell line-derived neurotrophic factor (GDNF)
* Neurturin
* Persephin
* Artemin
* Growth differentiation factor-9 (GDF9)
* Hepatocyte growth factor (HGF)
* Hepatoma-derived growth factor (HDGF)
* Insulin
* Insulin-like growth factors
* Insulin-like growth factor-1 (IGF-1)
* Insulin-like growth factor-2 (IGF-2)
* Interleukins
* IL-1\- Cofactor for IL-3 and IL-6. Activates T cells.
* IL-2 – T-cell growth factor. Stimulates IL-1 synthesis. Activates B-cells and NK cells.
* IL-3 – Stimulates production of all non-lymphoid cells.
* IL-4 – Growth factor for activated B cells, resting T cells, and mast cells.
* IL-5 – Induces differentiation of activated B cells and eosinophils.
* IL-6 – Stimulates Ig synthesis. Growth factor for plasma cells.
* IL-7 – Growth factor for pre-B cells.
* Keratinocyte growth factor (KGF)
* Migration-stimulating factor (MSF)
* Macrophage-stimulating protein (MSP), also known as hepatocyte growth factor-like protein (HGFLP)
* Myostatin (GDF-8)
* Neuregulins
* Neuregulin 1 (NRG1)
* Neuregulin 2 (NRG2)
* Neuregulin 3 (NRG3)
* Neuregulin 4 (NRG4)
* Neurotrophins
* Brain-derived neurotrophic factor (BDNF)
* Nerve growth factor (NGF)
* Neurotrophin-3 (NT-3)
* Neurotrophin-4 (NT-4)
* Placental growth factor (PGF)
* Platelet-derived growth factor (PDGF)
* Renalase (RNLS) – Anti-apoptotic survival factor
* T-cell growth factor (TCGF)
* Thrombopoietin (TPO)
* Transforming growth factors
* Transforming growth factor alpha (TGF-α)
* Transforming growth factor beta (TGF-β)
* Tumor necrosis factor-alpha (TNF-α)
* Vascular endothelial growth factor (VEGF)

## In platelets

[edit]

The alpha granules in blood platelets contain growth factors PDGF, IGF-1, EGF, and TGF-β which begin healing of wounds by attracting and activating macrophages, fibroblasts, and endothelial cells.

## Uses in medicine

[edit]

For the last two decades, growth factors have been increasingly used in the treatment of hematologic and oncologic diseases[4][5] and cardiovascular diseases[6][7] such as:

* skin wound healing and regeneration of other tissues such as bone (PDGF-BB)
* neutropenia
* myelodysplastic syndrome (MDS)
* leukemias
* aplastic anaemia
* bone marrow transplantation
* angiogenesis for cardiovascular diseases

## See also

[edit]

* Angiogenesis
* Bone growth factor
* Cytokine
* Growth factor receptor
* Human Genome Organisation
* Mitogen
* Neurotrophic factor
* Receptor (biochemistry)
* Signal transduction
* Wound healing § Overview of involved growth factors

## References

[edit]

1. ^ "growth factor" at Dorland's Medical Dictionary
2. ^ Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, Márquez-M M, De la Garza-Ramos MA (September 2015). "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine. 11: 29. doi:10.1186/s13005-015-0086-5. PMC 4558932. PMID 26334535.
3. ^ Yorio T, Clark AF, Wax MB (2007). Ocular Therapeutics: Eye on New Discoveries. Academic Press. p. 88\. ISBN 978-0-12-370585-3.
4. ^ Cottler-Fox M, Klein HG (April 1994). "Transfusion support of hematology and oncology patients. The role of recombinant hematopoietic growth factors". Archives of Pathology & Laboratory Medicine. 118 (4): 417–20\. PMID 7909429.
5. ^ Aaronson SA (November 1991). "Growth factors and cancer". Science. 254 (5035): 1146–53\. Bibcode:1991Sci...254.1146A. doi:10.1126/science.1659742. PMID 1659742.
6. ^ Domouzoglou EM, Naka KK, Vlahos AP, Papafaklis MI, Michalis LK, Tsatsoulis A, Maratos-Flier E (September 2015). "Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21". American Journal of Physiology. Heart and Circulatory Physiology. 309 (6): H1029-38. doi:10.1152/ajpheart.00527.2015. PMC 4747916. PMID 26232236.
7. ^ Gorenoi, Vitali; Brehm, Michael U.; Koch, Armin; Hagen, Anja (2017). "Growth factors for angiogenesis in peripheral arterial disease". The Cochrane Database of Systematic Reviews. 2017 (6): CD011741. doi:10.1002/14651858.CD011741.pub2. ISSN 1469-493X. PMC 6481523. PMID 28594443.

## External links

[edit]

* Growth+Factors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
* FGF5 in Hair Tonic Products
* FGF1 in Cosmetic Products

* v
* t
* e

Growth factors

Fibroblast|

| FGF receptor ligands:|

* FGF1/FGF2/FGF5
* FGF3/FGF4/FGF6

|

KGF|

* FGF7/FGF10/FGF22
* FGF8/FGF17/FGF18
* FGF9/FGF16/FGF20

FGF homologous factors:|

* FGF11(FHF3)
* FGF12(FHF1)
* FGF13(FHF2)
* FGF14(FHF4)

hormone-like: FGF15/19|

* FGF15
* FGF19
* FGF21
* FGF23

EGF-like domain|

* TGFα
* EGF
* HB-EGF

TGFβ pathway|

* TGFβ
* TGFβ1
* TGFβ2
* TGFβ3

Insulin/IGF/
Relaxin family|

| Insulin and Insulin-like growth factor|

* IGF1
* IGF2

|

Relaxin family peptide hormones|

* INSL3
* INSL4
* INSL5
* INSL6
* Relaxin
* 1
* 2
* 3

Platelet-derived|

* PDGFA
* PDGFB
* PDGFC
* PDGFD

Vascular endothelial|

* VEGF-A
* VEGF-B
* VEGF-C
* VEGF-D
* PGF

Other|

* Nerve
* Hepatocyte

* v
* t
* e

Cell signaling: cytokines

By family|

| Chemokine|

| CCL|

* CCL1
* CCL2/MCP1
* CCL3/MIP1α
* CCL4/MIP1β
* CCL5/RANTES
* CCL6
* CCL7
* CCL8
* CCL9
* CCL11
* CCL12
* CCL13
* CCL14
* CCL15
* CCL16
* CCL17
* CCL18/PARC/DCCK1/AMAC1/MIP4
* CCL19
* CCL20
* CCL21
* CCL22
* CCL23
* CCL24
* CCL25
* CCL26
* CCL27
* CCL28

|

CXCL|

* CXCL1/KC
* CXCL2
* CXCL3
* CXCL4
* CXCL5
* CXCL6
* CXCL7
* CXCL8/IL8
* CXCL9
* CXCL10
* CXCL11
* CXCL12
* CXCL13
* CXCL14
* CXCL15
* CXCL16
* CXCL17

CX3CL|

* CX3CL1

XCL|

* XCL1
* XCL2

TNF|

* TNFA
* Lymphotoxin
* TNFB/LTA
* TNFC/LTB
* TNFSF4
* TNFSF5/CD40LG
* TNFSF6
* TNFSF7
* TNFSF8
* TNFSF9
* TNFSF10
* TNFSF11
* TNFSF13
* TNFSF13B
* EDA

Interleukin|

| Type I
(grouped by
receptor
subunit)|

| γ chain|

* IL2/IL15
* IL4/IL13
* IL7
* IL9
* IL21

|

β chain|

* IL3
* IL5
* GMCSF

IL6 like/gp130|

* IL6
* IL11
* IL27
* IL30
* IL31
* +non IL OSM
* LIF
* CNTF
* CTF1

IL12 family/IL12RB1|

* IL12
* IL23
* IL27
* IL35

Other|

* IL14
* IL16
* IL32
* IL34

Type II|

| IL10 family|

* IL10/IL22
* IL19
* IL20
* IL24
* IL26
* Interferon type III
* IL28/IFNL2+3
* IL29/IFNL1

|

Interferon|

| I|

* IFNA1
* IFNA2
* IFNA4
* IFNA5
* IFNA6
* IFNA7
* IFNA8
* IFNA10
* IFNA13
* IFNA14
* IFNA16
* IFNA17
* IFNA21
* IFNB1
* IFNK
* IFNW1

|

II|

* IFNG

Ig superfamily|

* IL1 family: IL1A/IL1F1
* IL1B/IL1F2
* 1Ra/IL1F3
* IL1F5
* IL1F6
* IL1F7
* IL1F8
* IL1F9
* IL1F10
* 33/IL1F11
* 18/IL1G

IL17 family|

* IL17/IL25 (IL17A)

Other|

* Hematopoietic
* KITLG
* Colony-stimulating factor
* SPP1
* MIF

By function/
cell|

* proinflammatory cytokine
* IL1
* TNFA

* Monokine
* Lymphokine
* Th1
* IFNγ
* TNFβ
* Th2
* IL4
* IL5
* IL6
* IL10
* IL13

* v
* t
* e

Wound healing

* Fibrosis
* Maggot therapy
* Granulation tissue
* Growth factor
* Scar
* Stem cell
* Angiogenesis
* Intussusception
* Vasculogenesis

* v
* t
* e

Growth factor receptor modulators

Angiopoietin|

* Agonists: Angiopoietin 1
* Angiopoietin 4

* Antagonists: Angiopoietin 2
* Angiopoietin 3

* Kinase inhibitors: Altiratinib
* CE-245677
* Rebastinib

* Antibodies: Evinacumab (against angiopoietin 3)
* Nesvacumab (against angiopoietin 2)

CNTF|

* Agonists: Axokine
* CNTF
* Dapiclermin

EGF (ErbB)|

| EGF
(ErbB1/HER1)|

* Agonists: Amphiregulin
* Betacellulin
* EGF (urogastrone)
* Epigen
* Epiregulin
* Heparin-binding EGF-like growth factor (HB-EGF)
* Murodermin
* Nepidermin
* Transforming growth factor alpha (TGFα)

* Kinase inhibitors: Afatinib
* Agerafenib
* Brigatinib
* Canertinib
* Dacomitinib
* Erlotinib
* Gefitinib
* Grandinin
* Icotinib
* Lapatinib
* Neratinib
* Osimertinib
* Vandetanib
* WHI-P 154

* Antibodies: Cetuximab
* Depatuxizumab
* Depatuxizumab mafodotin
* Futuximab
* Imgatuzumab
* Matuzumab
* Necitumumab
* Nimotuzumab
* Panitumumab
* Zalutumumab

|

ErbB2/HER2|

* Agonists: Unknown/none

* Antibodies: Ertumaxomab
* Pertuzumab
* Trastuzumab
* Trastuzumab deruxtecan
* Trastuzumab duocarmazine
* Trastuzumab emtansine

* Kinase inhibitors: Afatinib
* Lapatinib
* Mubritinib
* Neratinib
* Tucatinib

ErbB3/HER3|

* Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C))

* Antibodies: Duligotumab
* Patritumab
* Seribantumab

ErbB4/HER4|

* Agonists: Betacellulin
* Epigen
* Heparin-binding EGF-like growth factor (HB-EGF)
* Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))

FGF|

| FGFR1|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20)
* Repifermin
* Selpercatinib
* Trafermin
* Velafermin

|

FGFR2|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22)
* Palifermin
* Repifermin
* Selpercatinib
* Sprifermin
* Trafermin

* Antibodies: Aprutumab
* Aprutumab ixadotin

* Kinase inhibitors: Infigratinib

FGFR3|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 4, 8, 9, 18, 23)
* Selpercatinib
* Sprifermin
* Trafermin

* Antibodies: Burosumab (against FGF23)

FGFR4|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 4, 6, 8, 9, 19)
* Trafermin

Unsorted|

* Agonists: FGF15/19

HGF (c-Met)|

* Agonists: Fosgonimeton
* Hepatocyte growth factor

* Potentiators: Dihexa (PNB-0408)

* Kinase inhibitors: Altiratinib
* AM7
* AMG-458
* Amuvatinib
* BMS-777607
* Cabozantinib
* Capmatinib
* Crizotinib
* Foretinib
* Golvatinib
* INCB28060
* JNJ-38877605
* K252a
* MK-2461
* PF-04217903
* PF-2341066
* PHA-665752
* SU-11274
* Tivantinib
* Volitinib

* Antibodies: Emibetuzumab
* Ficlatuzumab
* Flanvotumab
* Onartuzumab
* Rilotumumab
* Telisotuzumab
* Telisotuzumab vedotin

IGF|

| IGF-1|

* Agonists: des(1-3)IGF-1
* Insulin-like growth factor-1 (somatomedin C)
* IGF-1 LR3
* Insulin-like growth factor-2 (somatomedin A)
* Insulin
* Mecasermin
* Mecasermin rinfabate

* Kinase inhibitors: BMS-754807
* Linsitinib
* NVP-ADW742
* NVP-AEW541
* OSl-906

* Antibodies: AVE-1642
* Cixutumumab
* Dalotuzumab
* Figitumumab
* Ganitumab
* Robatumumab
* R1507
* Teprotumumab
* Xentuzumab (against IGF-1 and IGF-2)

|

IGF-2|

* Agonists: Insulin-like growth factor-2 (somatomedin A)

* Antibodies: Dusigitumab
* Xentuzumab (against IGF-1 and IGF-2)

Others|

* Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7)

* Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1)
* Trofinetide

LNGF (p75NTR)|

* Agonists: BDNF
* BNN-20
* BNN-27
* Cenegermin
* DHEA
* DHEA-S
* NGF
* NT-3
* NT-4

* Antagonists: ALE-0540
* Dexamethasone
* EVT-901 (SAR-127963)
* Testosterone

* Antibodies: Against NGF: ABT-110 (PG110)
* ASP-6294
* Fasinumab
* Frunevetmab
* Fulranumab
* MEDI-578
* Ranevetmab
* Tanezumab

* Aptamers: Against NGF: RBM-004

* Decoy receptors: LEVI-04 (p75NTR-Fc)

PDGF|

* Agonists: Becaplermin
* Platelet-derived growth factor (A, B, C, D)

* Kinase inhibitors: Agerafenib
* Avapritinib
* Axitinib
* Crenolanib
* Imatinib
* Lenvatinib
* Masitinib
* Motesanib
* Nintedanib
* Pazopanib
* Radotinib
* Quizartinib
* Ripretinib
* Sunitinib
* Sorafenib
* Toceranib

* Antibodies: Olaratumab
* Ramucirumab
* Tovetumab

RET (GFL)|

| GFRα1|

* Agonists: Glial cell line-derived neurotrophic factor (GDNF)
* Liatermin

* Kinase inhibitors: Vandetanib

|

GFRα2|

* Agonists: Neurturin (NRTN)

* Kinase inhibitors: Vandetanib

GFRα3|

* Agonists: Artemin (ARTN)

* Kinase inhibitors: Vandetanib

GFRα4|

* Agonists: Persephin (PSPN)

* Kinase inhibitors: Vandetanib

Unsorted|

* Kinase inhibitors: Agerafenib

SCF (c-Kit)|

* Agonists: Ancestim
* Stem cell factor

* Kinase inhibitors: Agerafenib
* Axitinib
* Dasatinib
* Imatinib
* Masitinib
* Nilotinib
* Pazopanib
* Quizartinib
* Sorafenib
* Sunitinib
* Toceranib

TGFβ|

* See here instead.

Trk|

| TrkA|

* Agonists: Amitriptyline
* BNN-20
* BNN-27
* Cenegermin
* DHEA
* DHEA-S
* Gambogic amide
* NGF
* Tavilermide

* Antagonists: ALE-0540
* Dexamethasone
* FX007
* Testosterone

* Negative allosteric modulators: VM-902A

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* Milciclib
* ONO-4474
* ONO-5390556
* PLX-7486
* Rebastinib
* SNA-120 (pegylated K252a))

* Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110)
* ASP-6294
* Fasinumab
* Frunevetmab
* Fulranumab
* MEDI-578
* Ranevetmab
* Tanezumab

* Aptamers: Against NGF: RBM-004

* Decoy receptors: ReN-1820 (TrkAd5)

|

TrkB|

* Agonists: 3,7-DHF
* 3,7,8,2'-THF
* 4'-DMA-7,8-DHF
* 7,3'-DHF
* 7,8-DHF
* 7,8,2'-THF
* 7,8,3'-THF
* Amitriptyline
* BDNF
* BNN-20
* Deoxygedunin
* Deprenyl
* Diosmetin
* DMAQ-B1
* HIOC
* LM22A-4
* N-Acetylserotonin
* NT-3
* NT-4
* Norwogonin (5,7,8-THF)
* R7
* R13
* TDP6

* Antagonists: ANA-12
* Cyclotraxin B
* Gossypetin (3,5,7,8,3',4'-HHF)

* Ligands: DHEA

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* ONO-4474
* ONO-5390556
* PLX-7486

TrkC|

* Agonists: BNN-20
* DHEA
* NT-3

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* ONO-4474
* ONO-5390556
* PLX-7486

VEGF|

* Agonists: Placental growth factor (PGF)
* Ripretinib
* Telbermin
* VEGF (A, B, C, D (FIGF))

* Allosteric modulators: Cyclotraxin B

* Kinase inhibitors: Agerafenib
* Altiratinib
* Axitinib
* Cabozantinib
* Cediranib
* Fruquintinib
* Lapatinib
* Lenvatinib
* Motesanib
* Nintedanib
* Pazopanib
* Pegaptanib
* Rebastinib
* Regorafenib
* Semaxanib
* Sorafenib
* Sunitinib
* Toceranib
* Tivozanib
* Vandetanib
* WHI-P 154

* Antibodies: Alacizumab pegol
* Bevacizumab
* Icrucumab
* Ramucirumab
* Ranibizumab

* Decoy receptors: Aflibercept

Others|

* Additional growth factors: Adrenomedullin
* Colony-stimulating factors (see here instead)
* Connective tissue growth factor (CTGF)
* Ephrins (A1, A2, A3, A4, A5, B1, B2, B3)
* Erythropoietin (see here instead)
* Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
* Glia maturation factor (GMF)
* Hepatoma-derived growth factor (HDGF)
* Interleukins/T-cell growth factors (see here instead)
* Leukemia inhibitory factor (LIF)
* Macrophage-stimulating protein (MSP; HLP, HGFLP)
* Midkine (NEGF2)
* Migration-stimulating factor (MSF; PRG4)
* Oncomodulin
* Pituitary adenylate cyclase-activating peptide (PACAP)
* Pleiotrophin
* Renalase
* Thrombopoietin (see here instead)
* Wnt signaling proteins

* Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)

Authority control databases

National|

* United States
* Japan
* Czech Republic
* Israel

Other|

* Yale LUX

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