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.
