Fibromodulin is a
protein that in humans is encoded by the FMODgene.[5][6]
Fibromodulin is a 42kDa
protein of a family of small interstitial leucine-rich repeat
proteoglycans (SLRPs). It can have up to four N-linked
keratan sulfate chains attached to the core protein within the leucine-rich region. It shares significant
sequence homology with
biglycan and
decorin.[7]
Function
Fibromodulin participates in the assembly of the collagen fibers of the extracellular matrix. It binds to the same site on the
collagen type I molecule as
lumican.[8] It also inhibits fibrillogenesis of
collagen type I and collagen type III in vitro.[9][10] It regulates TGF-beta activities by sequestering TGF-beta into the extracellular matrix.[6]
Clinical significance
There is an age-dependent decline in the synthesis of
keratan sulfate chains, so non-glycated forms of fibromodulin can accumulate in tissues such as
cartilage.[11]
Fibromodulin is found in the
epidermis of human
skin and is expressed by skin cells (
keratinocytes) in culture. Mice with the gene for fibromodulin knocked out (Fmod-/-) have very fragile
skin[12] and abnormal tail and
Achilles tendons.[13] The
collagen fiber bundles in these tendons are fewer and disorganised and there is less endotenon surrounding the tendon tissue. The levels of
lumican, a SLRP with one of the same collagen binding sites as fibromodulin, is increased 4 fold in the tail tendons of Fmod-knockout mice.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Sztrolovics R, Chen XN, Grover J, Roughley PJ, Korenberg JR (Mar 1995). "Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence". Genomics. 23 (3): 715–7.
doi:
10.1006/geno.1994.1567.
PMID7851907.
^Antonsson P, Heinegård D, Oldberg A (1993). "Structure and deduced amino acid sequence of the human fibromodulin gene". Biochim Biophys Acta. 1174 (2): 204–6.
doi:
10.1016/0167-4781(93)90117-V.
PMID8357838.
^Halper J (2014). "Proteoglycans and Diseases of Soft Tissues". Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology. Vol. 802. pp. 49–58.
doi:
10.1007/978-94-007-7893-1_4.
ISBN978-94-007-7892-4.
PMID24443020.
Roughley PJ, Lee ER (Aug 1994). "Cartilage proteoglycans: structure and potential functions". Microscopy Research and Technique. 28 (5): 385–97.
doi:
10.1002/jemt.1070280505.
PMID7919526.
S2CID43194492.
Gori F, Schipani E, Demay MB (2001). "Fibromodulin is expressed by both chondrocytes and osteoblasts during fetal bone development". Journal of Cellular Biochemistry. 82 (1): 46–57.
doi:
10.1002/jcb.1115.
PMID11400162.
S2CID41342892.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8.
Bibcode:
2005Natur.437.1173R.
doi:
10.1038/nature04209.
PMID16189514.
S2CID4427026.