Matrikine

Matrikines are a large and somewhat loosely defined group of peptides and small proteins, encompassing both endogenous signalling factors important in wound healing and tissue remodeling, and synthetically produced versions of these along with related analogues and derivatives, which are used mainly for cosmetic applications as well as for scientific research and with some medical indications.[1][2][3][4][5][6][7][8][9][10][11][12][13][14]

Classification

There are over 100 peptides which have been claimed as falling within this group, though most of them have relatively little published research and only a dozen or so such compounds are widely known and well characterised.[15] Most compounds referred to as matrikines are synthetic versions of peptide fragments 2-6 amino acids in length which are found in connective tissue proteins such as collagen, elastin, fibronectin and laminin, and were originally isolated as products of the enzymatic hydrolysis of these proteins. Many of these form naturally in the body following injury or tissue damage, and act as signalling factors which trigger tissue repair processes. Larger protein fragments cleaved from the full length connective tissue proteins, such as arresten, canstatin and tumstatin, also have similar functions and may be grouped along with the smaller peptide matrikines. There are also other peptide fragments which are commonly included in the matrikine group on the basis of their similar activity, despite not being derived from connective tissue proteins.

Function

Endogenous production of these peptides stimulates cells in the skin such as fibroblasts to synthesise more of the connective tissue proteins, and is claimed that administering the synthetic equivalent peptides can facilitate skin repair and wound healing and may have an anti-wrinkle and anti-aging effect. These peptides are administered topically as skin creams, or sometimes by subcutaneous injection or microneedling. Due to the poor absorption of even small peptides when administered topically to the skin, it is common for them to be conjugated with lipophilic chains such as palmitate or myristate to help them penetrate more deeply, though modern skin cream formulations often use more advanced techniques such as encapsulating them within liposomes which can achieve a similar effect. It is important to note that matrikines are a diverse class of signalling peptides which do not all have the same spectrum of activity; certain members of the family such as hexapeptide-12 actually have a primarily pro-aging effect and are used in research into the aging process rather than as ingredients of anti-aging skin creams. Other matrikines can have anti-aging effects at low concentrations but promote carcinogenesis and tumor growth at higher levels, so appropriate dosage control is critical.

Research and applications

Since matrikine peptides are used primarily for cosmetic applications which require only limited safety testing and have no requirement for proof of efficacy, much research into these peptides has been published in self-published sources such as patent applications, or in open-access journals which are generally regarded as low-quality sources due to the limited scope of peer review. This has meant that the claimed skin repair and anti-aging efficacy of these peptides has historically been treated with skepticism by the mainstream scientific community and regarded as marketing hype which has not been proven by rigorous scientific research. In recent years however, increasing evidence has accumulated to support the claimed activity of at least some of the matrikine peptides, along with investigation of these molecules for potential clinical applications such as treatment of arthritis and tendinopathy, and this has led medicines regulators in some jurisdictions such as Australia and New Zealand to view certain peptides from this group as medicines, and consequently ban them by classifying them as prescription medicines which are not actually available for prescription. In most parts of the world however these peptides are still classified as cosmetics and can be sold with relatively few restrictions, and they are widely used in countries such as Japan, China, South Korea, the United States and in Europe.

Examples

See also

References

  1. ^ Maquart, François-Xavier; Pasco, Sylvie; Ramont, Laurent; Hornebeck, William; Monboisse, Jean-Claude (2004). "An introduction to matrikines: Extracellular matrix-derived peptides which regulate cell activity". Critical Reviews in Oncology/Hematology. 49 (3): 199–202. doi:10.1016/j.critrevonc.2003.06.007. PMID 15036260.
  2. ^ Burgess, Janette K.; Weckmann, Markus (2012). "Matrikines and the lungs". Pharmacology & Therapeutics. 134 (3): 317–337. doi:10.1016/j.pharmthera.2012.02.002. PMID 22366287.
  3. ^ Grahovac, Jelena; Wells, Alan (2014). "Matrikine and matricellular regulators of EGF receptor signaling on cancer cell migration and invasion". Laboratory Investigation. 94 (1): 31–40. doi:10.1038/labinvest.2013.132. PMC 4038324. PMID 24247562.
  4. ^ Wells, J. Michael; Gaggar, Amit; Blalock, J. Edwin (2015). "MMP generated matrikines". Matrix Biology. 44–46: 122–129. doi:10.1016/j.matbio.2015.01.016. PMC 4838901. PMID 25636538.
  5. ^ Sivaraman, K.; Shanthi, C. (2018). "Matrikines for therapeutic and biomedical applications". Life Sciences. 214: 22–33. doi:10.1016/j.lfs.2018.10.056. PMID 30449450.
  6. ^ Ricard-Blum, Sylvie; Vallet, Sylvain D. (2019). "Fragments generated upon extracellular matrix remodeling: Biological regulators and potential drugs". Matrix Biology. 75–76: 170–189. doi:10.1016/j.matbio.2017.11.005. PMID 29133183.
  7. ^ Kisling, Andrew; Lust, Robert M.; Katwa, Laxmansa C. (2019). "What is the role of peptide fragments of collagen I and IV in health and disease?". Life Sciences. 228: 30–34. doi:10.1016/j.lfs.2019.04.042. PMID 31004660.
  8. ^ Jariwala, Nathan; Ozols, Matiss; Bell, Mike; Bradley, Eleanor; Gilmore, Andrew; Debelle, Laurent; Sherratt, Michael J. (2022). "Matrikines as mediators of tissue remodelling". Advanced Drug Delivery Reviews. 185 114240. doi:10.1016/j.addr.2022.114240. PMID 35378216.
  9. ^ Mohindra, Ritika; Mohindra, Rohit; Agrawal, Devendra K.; Thankam, Finosh G. (2022). "Bioactive extracellular matrix fragments in tendon repair". Cell and Tissue Research. 390 (2): 131–140. doi:10.1007/s00441-022-03684-z. PMID 36074173.
  10. ^ Rapp, Anna E.; Zaucke, Frank (2023). "Cartilage extracellular matrix-derived matrikines in osteoarthritis". American Journal of Physiology. Cell Physiology. 324 (2): C377–C394. doi:10.1152/ajpcell.00464.2022. PMID 36571440.
  11. ^ Chen, Kaiqi; Xu, Mimi; Lu, Feng; He, Yunfan (2023). "Development of Matrix Metalloproteinases-Mediated Extracellular Matrix Remodeling in Regenerative Medicine: A Mini Review". Tissue Engineering and Regenerative Medicine. 20 (5): 661–670. doi:10.1007/s13770-023-00536-x. PMC 10352474. PMID 37160567.
  12. ^ Revert-Ros, Francisco; Ventura, Ignacio; Prieto-Ruiz, Jesús A.; Hernández-Andreu, José Miguel; Revert, Fernando (2024). "The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen". International Journal of Molecular Sciences. 25 (12): 6523. doi:10.3390/ijms25126523. PMC 11203716. PMID 38928229.
  13. ^ Sirois, Jonathan P.; Heinz, Andrea (2024). "Matrikines in the skin: Origin, effects, and therapeutic potential". Pharmacology & Therapeutics. 260 108682. doi:10.1016/j.pharmthera.2024.108682. PMID 38917886.
  14. ^ Ostadi, Yasamin; Khanali, Javad; Tehrani, Fatemeh A.; Yazdanpanah, Ghasem; Bahrami, Soheyl; Niazi, Feizollah; Niknejad, Hassan (2024). "Decellularized Extracellular Matrix Scaffolds for Soft Tissue Augmentation: From Host–Scaffold Interactions to Bottlenecks in Clinical Translation". Biomaterials Research. 28 0071. doi:10.34133/bmr.0071. PMC 11378302. PMID 39247652.
  15. ^ Van Walraven, Nathalie; Fitzgerald, Richard J.; Danneel, Hans-Jürgen; Amigo-Benavent, Miryam (2025). "Bioactive peptides in cosmetic formulations: Review of current in vitro and ex vivo evidence". Peptides. 193 171440. doi:10.1016/j.peptides.2025.171440. PMID 40946970.