MARINE INGREDIENTS
Marine minerals in the dermal matrisome
Brian Fitzpatrick – Oriel Marine R&D Dr Chunxu Shan, Paul Tolan, Dr Bernard Degryse, Dr Ronan P. Murphy - Dublin City University Patrick Bourke - Safeguard Medical Dr Andrea Mitarotonda - Independent consultant
In recent decades, both anti-ageing and biomedical research have focused intensely on the biochemistry and pathophysiology of the extra-cellular matrix (ECM), as well as on matrix dysregulation, which can underpin skin pathophysiology.1,2
space and is present in all connective tissues including that of the integumentary system. Within the intercellular space, phenomena
like cellular polarisation and migration, regulation of growth factors, activation and modulation of signalling transduction and gene expression, and processes translating mechanical stimulation into a biochemical signal through the involvement of mechanosensitive channels are all essential for the maintenance of ECM elasticity, dermal tissue architecture and tone. Mechano-transduction in particular, is an increasingly well-studied process, and regulates cellular ‘tensegrity’, an emerging field of mechanobiology.3
Hyaluronic acid One molecule in particular has emerged as a key player in ECM biology, despite not being one of the ‘core-matrisome’ group: hyaluronic acid (HA).4,5
The ECM fills the intercellular
91
Figure 1: Representative scatter plot of ECM gene regulation
of inflammatory cells to enhance immune response and the response to injury of fibroblasts and epithelial cells. The size of HA appears to be of critical
HA is a non-sulphated
glycosaminoglycan (GAG) and is composed of repeating polymeric disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine linked by a glucuronidic β (1→3) bond. In aqueous solutions, HA forms specific,
stable, tertiary structures. Despite the simplicity of its composition, without variations in its sugar composition or branching points, it has a myriad of physiological properties. HA polymers occur in many configurations and shapes, depending on their size, salt concentration, pH and associated cations. Unlike other GAGs, HA is not covalently
attached to a protein core, but forms aggregates with proteoglycans. It has a high affinity for and encompasses a large volume of water, giving solutions high viscosity, even at low concentrations. The skin contains 50% of the HA in the body, and it is produced by many skin cell types, including keratinocytes and dermal fibroblasts. The biological functions of HA include
hydration and the intra-cellular framework through which cells exist and function. HA synthesis increases during tissue injury and wound healing and it regulates several aspects of tissue repair, including activation
www.personalcaremagazine.com
importance for its various biological functions. HA of high molecular size, usually in excess of 1,000kDa, is present in intact tissues and is anti-angiogenic and immune-suppressive, whereas smaller polymers are distress signals and potent inducers of inflammation and angiogenesis. HA is synthesised on the inner surface of the plasma membrane by specific membrane-bound enzymes called HA synthases (HASs), then extruded through pore-like structures into the extracellular space. There are three mammalian enzymes, HAS-1, -2 and -3, which all exhibit distinct enzymatic properties and synthesise HA chains of various length. HA has a dynamic turnover rate, with a half-
life of three to five minutes in blood, less than 24 hours in the skin and up to three weeks in cartilage. It is degraded into fragments of varying size by hyaluronidases (HYALs). Six human HYALs have been identified so far: HYAL-1, -2, -3, -4, PH- 20 and HYALP1. Until recently, these were not well characterised, due to their low concentrations, difficulties in purification, and challenges in studying their kinetics and dynamics. HA can also be degraded non-enzymatically
by a free-radical mechanism in the presence of reducing agents and molecular oxygen. Thus,
agents that could delay this degradation may be useful in maintaining the integrity of dermal HA and its hydration properties. High-resolution microscopy has permitted the visualisation of HA in the epidermis, mainly in the ECM of the upper spinous and granular layers and the basal layer, where it is predominantly intracellular. Skin hydration critically depends on the HA-
bound water in the dermis and in the vital area of the epidermis, while maintaining hydration essentially depends on the stratum granulosum. The HA content of the dermis is significantly higher than that of the epidermis, while the papillary dermis has much greater levels than the reticular dermis. The HA of the dermis is in continuity with the
lymphatic and vascular systems. HA in the dermis regulates water balance, osmotic pressure and ion flow. It functions as a sieve, excluding certain molecules, enhancing the extracellular domain of cell surfaces and stabilising skin structures by electrostatic interactions. Elevated levels of HA are synthesised during
scar-free foetal tissue repair and its prolonged presence assures this repair. Both dermal fibroblasts and keratinocytes synthesise dermal HA and should be the target for pharmacologic attempts to enhance skin hydration. Unfortunately, exogenous HA is cleared from the dermis and rapidly degraded. It has been demonstrated that the three HAS isoforms are independently regulated
April 2022 PERSONAL CARE
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116
