Dermatopontin
| DPT | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | DPT, TRAMP, dermatopontin | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 125597; MGI: 1928392; HomoloGene: 1458; GeneCards: DPT; OMA:DPT - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Dermatopontin also known as tyrosine-rich acidic matrix protein (TRAMP) is a protein that in humans is encoded by the DPT gene.[5][6] Dermatopontin is a 22-kDa protein of the noncollagenous extracellular matrix (ECM) estimated to comprise 12 mg/kg of wet dermis weight.[7] To date, homologues have been identified in five different mammals and 12 different invertebrates with multiple functions.[8] In vertebrates, the primary function of dermatopontin is a structural component of the ECM (interaction with decorin and modification of collagen fibrillogenesis), cell adhesion, modulation of TGF-β activity and cellular quiescence). It also has pathological involvement in heart attacks (increased expression around myocardial infarct zone) and decreased expression in leiomyoma and fibrosis. In invertebrate, dermatopontin homologue plays a role in hemagglutination, cell-cell aggregation, and expression during parasite infection.[8]
Cellular and tissue distribution
[edit]Dermatopontin is expressed in the extracellular matrix (ECM), which is a gel-like fluid space outside of a cell that consists of collagen fibers, elastin fibers, glycoproteins, and proteoglycans (1). The components of the ECM are connected to proteins embedded in the plasma membrane of cells. These membrane proteins perform many functions, including transporting materials, serving as enzymes for chemical reactions, transmitting cell signals, and intercellular junction (1).
Dermatopontins are expressed primarily in fibroblasts, heart tissue, skeletal muscle, brain and pancreas. They occur less frequently in lungs and kidneys, and much less frequently in fibroblasts from hypertrophic scar lesional skin and in fibroblasts from patients with systemic sclerosis than in normal skin fibroblasts (3).
In the skin, DPT is found in the collagen fibers and also in the cytoplasm of cultured fibroblasts.”[8] DPT has also been found in the cornea, specifically the stroma.
The protein is found in various tissues and many of its tyrosine residues are sulphated.[6]
Function
[edit]Dermatopontin is a component of the intercellular junction that holds membranes of adjacent cells together (2). The components of the ECM are connected to proteins embedded in the plasma membrane, which in turn are connected to the internal cytoskeleton of the cell. These connections also facilitate cell-to-cell communication (1).
Dermatopontin mediates adhesion by cell surface integrin binding and accelerates collagen fibril formation that determines the size and arrangement of collagen fibrils within the extracellular matrix (2). Other functions of dermatopontin include stabilizing collagen fibrils against low temperature dissociation, inhibiting cell proliferation, enhancing TGFB1 activity, and possibly serving as a communication link between the dermal fibroblast cell surface and its extracellular environment (3).
Dermatopontin itself is a noncollagenous ECM protein but it facilitates collagen binding (2).
Dermatopontin is an extracellular matrix protein with possible functions in cell-matrix interactions and matrix assembly. The extracellular matrix (ECM) is known as a non-cellular component that is found in all organs and tissues. The ECM provides not only a physical scaffolding for individual cells, but also biomechanical communication between cells that is required for morphogenesis, differentiation and homeostasis.[9] One of the major roles of Dermatopontin includes its ability to promote cell adhesion. Since DPT is a proteoglycan binding protein, this helps in the adhesion between fibroblasts and keratinocytes. Dermatopontin (DPT) has a high expression of dermis and is part of the non-collagenous matrix. DPT also has an important role in activating transforming growth factor beta 1 (TGF-β1). TGF-β1 has an important role in wound healing.[7]
Re-epithelialization is also an important part of healing wounds. Both DPT and re-epithelialization depend on the migration of the epidermal keratinocytes and the many different growth factors that are located within the extracellular matrix. DPT was found able to aid in the migration of keratinocytes, but failed in the ability to induce cellular proliferation. The keratinocytes are epidermal cells that help with the production of keratin, which is a fibrous protein that can be found in hair, feathers, and hooves.
In the skin, DPT is found in the collagen fibers and also in the cytoplasm of cultured fibroblasts.” [8] DPT has also been found in the cornea, specifically the stroma.
Dermatopontin is postulated to modify the behavior of TGF beta through interaction with decorin.[6]
Cell adhesion
[edit]Cell adhesion is the effect of the cell behavior due to the function of the dermatopontin. Even though, cell adhesion activity of dermatopontin isn't strong for a certain fibroblasts and neurogenic cells, but it might have various roles in wound healings because dermatopontin has been found in a provisional matrix that interacted with fibrin and fibronectin (Fn) which has improved the cell adhesion activity of Fn.[8] A provisional matrix is forms of extravasated blood after the wounding, which compose of the wound fluid, fibrin and Fn. In the provisional matrix, the Fn perform as an adhesion and migration structure to provide support all around the ECM for fibroblasts and circulation-derived cells, while in tissues, Fn perform as an activated and collected into the Fn matrix (a fibrillar structure) that discovered during both development of embryonic and wound healing.[8] Dermatopontin has been found in the provisional matrix as well as in the wound fluid, and it has demonstrated that dermatopontin promoted Fn fibril formation that biologically functions in the dermal wound healing, and the presence of dermatopontin has enhanced the Fn interaction with fibrin as well as the enhancement of cell adhesion, which indicated the morphological changed of the cells that has been adhered to the complex.[10] Dermatopontin determined to be found in the interaction sites of Fn on III_13 and III_14 and cryptic site of III_1, which all involved in formation of Fn fibrils, and the inhibition of dermatopontin were considering to be between III_(2-3) and III_(12-14) because dermatopontin was not enhanced the interaction between III_(1-5) and III_(1-2), which could be the domains unfold as the disruption of the other interdomain interactions.[10] In this case, dermatopontin indicated as domain unfolding of a Fn molecule due to the binding site for anastellin (the only known protein that induce superfibronectin formation) on Fn is located between III_(2-3) and III_(12-14) inside the interaction site, which is the important binding site for the Fn fibril formation.[10] Therefore, dermatopontin is protein within the ECM that could activate Fn and induce Fn fibril formation, which could help in wound healing due to its accumulation in the wound whether from the ECM's surrounded or from the serum.
Applications
[edit]Dermatopontin plays a key role in interactions of the cell matrix and its assembly that can in turn induce cellular apoptosis. In the osteosarcoma MG-63 cell line, silencing the DPT gene decreased the proliferation of the MG-63 cells.[11][unreliable medical source]
DPT, along with lumican and decorin, is a biomarker for giant-cell tumor of bone (GCTB).[12][unreliable medical source]
There is also a relationship between CCW (chronic cutaneous wound) and the DPT gene. The healing of CCW can be inhibited through the destruction of some matrix proteins, such as DPT and low levels of DTP expression slows the rate of healing.[13][unreliable medical source]
DPT is also a biomarker for OSCC (oral squamous cell carcinoma) as well. It was shown that OSCC cells had a suppressed response to DPT. DPT expression had an inverse relationship with cellular adhesion, and a direct relationship with its invasiveness.[14][unreliable medical source]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000143196 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026574 – Ensembl, May 2017
- ^ "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.
- ^ Superti-Furga A, Rocchi M, Schäfer BW, Gitzelmann R (August 1993). "Complementary DNA sequence and chromosomal mapping of a human proteoglycan-binding cell-adhesion protein (dermatopontin)". Genomics. 17 (2): 463–7. doi:10.1006/geno.1993.1348. PMID 8104875.
- ^ a b c "Entrez Gene: DPT dermatopontin".
- ^ a b Krishnaswamy VR, Korrapati PS (December 2014). "Role of dermatopontin in re-epithelialization: implications on keratinocyte migration and proliferation". Scientific Reports. 4: 7385. Bibcode:2014NatSR...4E7385K. doi:10.1038/srep07385. PMC 4260223. PMID 25486882.
- ^ a b c d e f Okamoto O, Fujiwara S (2006). "Dermatopontin, a novel player in the biology of the extracellular matrix". Connective Tissue Research. 47 (4): 177–89. doi:10.1080/03008200600846564. PMID 16987749. S2CID 23944137.
- ^ Frantz C, Stewart KM, Weaver VM (December 2010). "The extracellular matrix at a glance". Journal of Cell Science. 123 (Pt 24): 4195–200. doi:10.1242/jcs.023820. PMC 2995612. PMID 21123617.
- ^ a b c Kato A, Okamoto O, Ishikawa K, Sumiyoshi H, Matsuo N, Yoshioka H, Nomizu M, Shimada T, Fujiwara S (April 2011). "Dermatopontin interacts with fibronectin, promotes fibronectin fibril formation, and enhances cell adhesion". The Journal of Biological Chemistry. 286 (17): 14861–9. doi:10.1074/jbc.M110.179762. PMC 3083196. PMID 21398523.
- ^ Xi LC, Ji YX, Yin D, Zhao ZX, Huang SC, Yu SL, Liu BY, Li HY (January 2018). "Effects of Dermatopontin gene silencing on apoptosis and proliferation of osteosarcoma MG‑63 cells". Molecular Medicine Reports. 17 (1): 422–427. doi:10.3892/mmr.2017.7866. PMID 29115446.
- ^ Lieveld M, Bodson E, De Boeck G, Nouman B, Cleton-Jansen AM, Korsching E, Benassi MS, Picci P, Sys G, Poffyn B, Athanasou NA, Hogendoorn PC, Forsyth RG (December 2014). "Gene expression profiling of giant cell tumor of bone reveals downregulation of extracellular matrix components decorin and lumican associated with lung metastasis". Virchows Archiv. 465 (6): 703–13. doi:10.1007/s00428-014-1666-7. hdl:1887/105336. PMID 25304290. S2CID 24625787.
- ^ Krishnaswamy VR, Manikandan M, Munirajan AK, Vijayaraghavan D, Korrapati PS (December 2014). "Expression and integrity of dermatopontin in chronic cutaneous wounds: a crucial factor in impaired wound healing". Cell and Tissue Research. 358 (3): 833–41. doi:10.1007/s00441-014-2000-z. PMID 25260909. S2CID 16355532.
- ^ Yamatoji M, Kasamatsu A, Kouzu Y, Koike H, Sakamoto Y, Ogawara K, Shiiba M, Tanzawa H, Uzawa K (June 2012). "Dermatopontin: a potential predictor for metastasis of human oral cancer". International Journal of Cancer. 130 (12): 2903–11. doi:10.1002/ijc.26328. PMID 21796630.
Further reading
[edit]- Pochampally RR, Ylostalo J, Penfornis P, Matz RR, Smith JR, Prockop DJ (September 2007). "Histamine receptor H1 and dermatopontin: new downstream targets of the vitamin D receptor". Journal of Bone and Mineral Research. 22 (9): 1338–49. doi:10.1359/jbmr.070605. PMID 17547532.
- Shaheduzzaman S, Krishnan V, Petrovic A, Bittner M, Meltzer P, Trent J, Venkatesan S, Zeichner S (2002). "Effects of HIV-1 Nef on cellular gene expression profiles". Journal of Biomedical Science. 9 (1): 82–96. doi:10.1007/BF02256581. PMID 11810028.
- Kuroda K, Okamoto O, Shinkai H (May 1999). "Dermatopontin expression is decreased in hypertrophic scar and systemic sclerosis skin fibroblasts and is regulated by transforming growth factor-beta1, interleukin-4, and matrix collagen". The Journal of Investigative Dermatology. 112 (5): 706–10. doi:10.1046/j.1523-1747.1999.00563.x. PMID 10233760.
- Okamoto O, Fujiwara S, Abe M, Sato Y (February 1999). "Dermatopontin interacts with transforming growth factor beta and enhances its biological activity". The Biochemical Journal. 337 ( Pt 3) (3): 537–41. doi:10.1042/0264-6021:3370537. PMC 1220007. PMID 9895299.
- Forbes EG, Cronshaw AD, MacBeath JR, Hulmes DJ (September 1994). "Tyrosine-rich acidic matrix protein (TRAMP) is a tyrosine-sulphated and widely distributed protein of the extracellular matrix". FEBS Letters. 351 (3): 433–6. doi:10.1016/0014-5793(94)00907-4. PMID 8082810.