Fibroblast growth factor 18

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Fibroblast growth factor 18
Properties of human protein
Mass / length primary structure 180 amino acids
Identifier
Gene name FGF18
External IDs
Occurrence
Parent taxon Vertebrates

The fibroblast growth factor 18 ( FGF-18 , of Engl. Fibroblast Growth Factor 18 ) is a signaling protein of the family of Fibroblast Growth Factors , which in vertebrates occurs.

genetics

In humans, the FGF18 gene coding for FGF-18 is located on chromosome 5 gene locus q34. It was first described in 1998 and consists of 1999 base pairs . The gene exists in mouse , rat and man first of 207 amino acids . By post-translational modification of the first 27 amino acids - the signal peptide - cut off so that the remaining 180 amino acids, the free FGF-18 form. FGF-18 is likely glycosylated on one or two amino acids and therefore has a molecular mass of about 23 kDa .

In humans, the following sequence is given in the one -letter code : 

MYSAPSACTC LCLHFLLLCF QVQVLVA (Signalpeptid)
EEN VDFRIHVENQ TRARDDVSRK QLRLYQLYSR
TSGKHIQVLG RRISARGEDG DKYAQLLVET DTFGSQVRIK GKETEFYLCM NRKGKLVGKP
DGTSKECVFI EKVLENNYTA LMSAKYSGWY VGFTKKGRPR KGPKTRENQQ DVHFMKRYPK
GQPELQKPFK YTTVTKRSRR IRPTHPA

function

Like all members of the FGF family, FGF-18 is involved in a large number of biological processes, such as embryonic development , cell growth , morphogenesis , wound healing , and tumor growth and infiltration. In various model organisms , FGF-18 is a growth factor that stimulates the proliferation of various cell tissues, especially in the liver and small intestine .

In some tumors, such as colorectal carcinoma , the expression of FGF-18 is upregulated.

In the ossification (bone formation) and chondrogenesis ( cartilage formation ) seems FGF-18 to have an important stimulatory function.

Therapeutic potential

Due to its diverse functions in the development, potentially also in the prevention or treatment of diseases is FGF-18 is a promising target ( Target ). In the animal model, intra-articular injection (into the joint) of FGF-18 stimulated chondrogenesis to build up joint cartilage. This is a potential therapeutic approach for arthritic joints . A corresponding active ingredient (Sprifermin ( INN ), AS902330 or rhFGF-18 ( recombinantly produced human FGF-18)) is currently in clinical phase I and II .

Individual evidence

  1. ↑ Homologues at OMA
  2. ↑ NCBI genes: FGF18 fibroblast growth factor 18 (Homo sapiens).
  3. ^ A b c T. Haque, S. Nakada, RC Hamdy: A review of FGF18: Its expression, signaling pathways and possible functions during embryogenesis and post-natal development. In: Histology and histopathology Volume 22, Number 1, January 2007, pp. 97-105, PMID 17128416 . (Review).
  4. ↑ NCBI nucleotides: Homo sapiens fibroblast growth factor 18 (FGF18), mRNA.
  5. ↑ N. Ohbayashi, M. Hoshikawa, S. Kimura, M. Yamasaki, S. Fukui, N. Itoh: Structure and expression of the mRNA encoding a novel fibroblast growth factor, FGF-18. In: The Journal of biological chemistry Volume 273, Number 29, July 1998, pp. 18161-18164, PMID 9660775 .
  6. ^ G. von Heijne: A new method for predicting signal sequence cleavage sites. In: Nucleic acids research Volume 14, Number 11, June 1986, pp. 4683-4690, PMID 3714490 . PMC 311474 (free full text).
  7. ↑ G. Sonvilla, S. Allerstorfer, S. Stättner, J. Karner, M. Klimpfinger, H. Fischer, B. Grasl-Kraupp, K. Holzmann, W. Berger, F. Wrba, B. Marian, M. Grusch : FGF18 in colorectal tumor cells: autocrine and paracrine effects. In: Carcinogenesis Volume 29, Number 1, January 2008, pp. 15-24, doi: 10.1093 / carcin / bgm202 . PMID 17890768 .
  8. ↑ N. Su, X. Du, L. Chen: FGF signaling: its role in bone development and human skeleton diseases. In: Frontiers in bioscience: a journal and virtual library Volume 13, 2008, pp. 2842-2865, PMID 17981758 . (Review).
  9. ↑ EE Moore, AM Bendele, DL Thompson, A. Littau, KS Waggie, B. Reardon, JL Ellsworth: Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. In: Osteoarthritis and Cartilage Volume 13, Number 7, July 2005, pp. 623-631, doi: 10.1016 / j.joca.2005.03.003 . PMID 15896984 .
  10. ↑ D. Davidson, A. Blanc, D. Filion, H. Wang, P. Plut, G. Pfeffer, MD Buschmann, JE Henderson: Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. In: The Journal of biological chemistry Volume 280, Number 21, May 2005, pp. 20509-20515, doi: 10.1074 / jbc.M410148200 . PMID 15781473 .
  11. ↑ Setback for Merck's pharmaceuticals business. In: FAZ of September 24, 2010
  12. ↑ clinicaltrials.gov: AS902330 in Cartilage Injury Repair (CIR). Retrieved January 30, 2011
  13. ↑ clinicaltrials.gov: Study of AS902330 (rhFGF-18) Administered Intra-articularly in Patients With Knee Primary Osteoarthritis Who Are Candidates for Total Knee Replacement. Retrieved January 30, 2011
  14. ↑ clinicaltrials.gov: A Multicenter Study of rhFGF 18 in Patients With Knee Osteoarthritis Not Requiring Surgery. Retrieved January 30, 2011

further reading

  • MC Hu, WR Qiu, YP Wang, D. Hill, BD Ring, S. Scully, B. Bolon, M. DeRose, R. Luethy, WS Simonet, T. Arakawa, DM Danilenko: FGF-18, a novel member of the fibroblast growth factor family, stimulates hepatic and intestinal proliferation. In: Molecular and cellular biology Volume 18, Number 10, October 1998, pp. 6063-6074, PMID 9742123 . PMC 109192 (free full text).