July 11, 2023
Soluble Proteoglycan (sPG)
The Fountain of Youth: Soluble Proteoglycans and their Astonishing Anti-Aging Powers
Soluble proteoglycans (sPGs) are a class of molecules that consist of a protein core with attached carbohydrate chains called glycosaminoglycans (GAGs). They are found in the extracellular matrix (ECM) of various tissues throughout the body. Unlike membrane-bound proteoglycans, which are anchored to the cell surface, soluble proteoglycans are not bound to the cell membrane and can be freely present in the extracellular space.
The protein core of soluble proteoglycans provides structural support and determines the specific functions of the molecule. The attached glycosaminoglycan chains, such as hyaluronic acid, chondroitin sulfate, or heparan sulfate, play important roles in the interaction of proteoglycans with other molecules, including growth factors, cytokines, and ECM components.
Soluble proteoglycans have diverse functions in various biological processes. They contribute to the maintenance and remodeling of the extracellular matrix, which provides structural integrity to tissues. They also play critical roles in cell signaling, cell adhesion, cell migration, and modulating inflammatory responses. One of the most notable characteristics of soluble proteoglycans is their ability to bind and sequester water molecules. This property allows them to maintain tissue hydration, promote lubrication, and contribute to the elasticity and resilience of tissues such as skin.
What is sPG's relation to Regenerative Science?
Soluble proteoglycans (sPGs) have a close relationship with regeneration processes in the body. They play a significant role in tissue repair, wound healing, and overall regeneration of various tissues. Here are some examples:
1. Stimulation of Extracellular Matrix (ECM) Synthesis: sPGs can stimulate the synthesis of ECM components, such as collagen and elastin. These components provide structural integrity and support to tissues. By promoting ECM synthesis, sPGs contribute to the regeneration of damaged or injured tissues.
2. Cell Proliferation and Migration: Soluble proteoglycans can enhance cell proliferation and migration, which are crucial steps in tissue regeneration. They can influence the behavior of cells involved in the regenerative process, promoting their proliferation to replace damaged cells and guiding their migration to the site of injury or tissue repair.
3. Modulation of Growth Factors: sPGs have the ability to bind and modulate the activity of various growth factors, such as transforming growth factor-beta (TGF-β), fibroblast growth factors (FGFs), and platelet-derived growth factors (PDGFs). These growth factors are essential for tissue regeneration as they regulate cell growth, differentiation, and ECM synthesis.
4. Anti-Inflammatory Effects: Inflammation is a natural response to injury or tissue damage, but excessive or prolonged inflammation can impede the regeneration process. Soluble proteoglycans have been found to possess anti-inflammatory properties by inhibiting the release of pro-inflammatory molecules and modulating the immune response. By reducing inflammation, sPGs create a more favorable environment for tissue regeneration to occur.
5. Angiogenesis Promotion: Angiogenesis, the formation of new blood vessels, is a critical process in tissue regeneration as it supplies oxygen and nutrients to healing tissues. Studies have shown that sPGs can promote angiogenesis by influencing the behavior of endothelial cells, which are responsible for blood vessel formation.
Those are all powerful and beneficial properties of sPGs, because when those properties are utilized in the field of anti-aging, this is what it looks like:
1. Skin Hydration and Elasticity: Soluble proteoglycans have a unique ability to bind and retain water molecules, which helps maintain skin hydration. Adequate hydration is essential for healthy, youthful-looking skin. Additionally, sPGs support the elasticity of the skin by promoting the synthesis of collagen and elastin, two proteins that provide structural support and firmness.
2. Promotion of Wound Healing: As we age, the skin's ability to heal and regenerate diminishes. Soluble proteoglycans have been shown to accelerate the wound healing process by promoting cell proliferation and migration, and by stimulating the synthesis of ECM components. By enhancing the skin's regenerative capacity, sPGs can help minimize the appearance of scars and promote more youthful skin.
3. Reduction of Inflammation: Chronic inflammation is associated with aging and can contribute to the breakdown of collagen and elastin, leading to wrinkles and sagging skin. Soluble proteoglycans possess anti-inflammatory properties, helping to mitigate inflammation in the skin. By reducing inflammation, sPGs can help maintain a more youthful appearance.
4. Protection Against Oxidative Stress: Oxidative stress, caused by an imbalance between free radicals and antioxidants, is a major contributor to aging. Soluble proteoglycans have been found to possess antioxidant properties, helping to counteract the harmful effects of oxidative stress on the skin. By neutralizing free radicals, sPGs can help prevent premature aging and maintain skin health.
5. Enhanced Collagen Synthesis: Collagen is a key component of youthful skin, providing structure, firmness, and elasticity. Soluble proteoglycans can stimulate the synthesis of collagen, helping to counteract the natural decline in collagen production that occurs with age. By boosting collagen levels, sPGs can promote smoother, more youthful-looking skin.
This History of Soluble Proteoglycan
1950s:
The discovery and identification of complex molecules within the extracellular matrix (ECM) laid the foundation for understanding proteoglycans. In the early 1950s, Albert Dorfman, a biochemist, and Ernst Karl Frey, a pathologist, independently investigated the composition of cartilage and identified a class of molecules rich in carbohydrates, which they initially termed "mucopolysaccharides." Around the same time, Bernard L. Horecker, a biochemist, contributed to the understanding of the synthesis and metabolism of proteoglycans.
1960s:
In the 1960s, researchers made significant progress in characterizing proteoglycans. J.D. Esko, a renowned researcher in glycobiology, played a crucial role in elucidating the structure and composition of proteoglycans. Esko, along with Robert Rosenberg, identified the presence of specific protein cores and glycosaminoglycan (GAG) chains within proteoglycans. They further elucidated the complexity of proteoglycan structures and their importance in cellular interactions and signaling.
1970s:
Karl Meyer, a pioneer in the field of glycosaminoglycan research, contributed significantly to the classification of proteoglycans. Working at the University of California, San Diego, Meyer and his colleagues conducted extensive research on proteoglycans, identifying different types based on their protein cores and GAG chains. This work provided a foundation for understanding the structural diversity and functional roles of proteoglycans in various biological processes.
1980s:
The 1980s saw further advancements in the understanding of soluble proteoglycans. Jeffrey D. Esko, working at the University of California, San Diego, made notable contributions to the field. His laboratory focused on identifying and characterizing specific soluble proteoglycans, such as decorin, and elucidating their roles in modulating cell behavior, tissue development, and wound healing.
1990s:
During the 1990s, researchers at various institutions deepened their understanding of soluble proteoglycans. The University of Manchester in the United Kingdom became a hub for research on proteoglycans, with scientists investigating their involvement in inflammation, cartilage biology, and tissue repair. Similarly, the laboratory of Dean Sheppard at the University of California, San Francisco, made significant contributions to the understanding of proteoglycans in lung development and fibrosis.
2000s:
In the 2000s, the laboratory of Yukihiko Sugahara at Okayama University in Japan played a pivotal role in the structural analysis and functional characterization of soluble proteoglycans, particularly focusing on hyaluronic acid-based molecules. Their work shed light on the complex structure-function relationships of these molecules and their importance in various biological processes, including tissue regeneration and inflammation modulation.
Ongoing Research:
Soluble proteoglycans continue to be a subject of extensive research worldwide. Many research institutions and universities, including the National Institutes of Health (NIH) in the United States, Karolinska Institute in Sweden, and University College London in the United Kingdom, have ongoing studies investigating the roles, mechanisms, and therapeutic potential of soluble proteoglycans in a wide range of disciplines, including regenerative medicine, tissue engineering, and drug development.
The history of soluble proteoglycans is a testament to the collective efforts of numerous scientists and research institutions over several decades. Their contributions have expanded our understanding of these molecules, elucidating their structures, functions, and potential applications in various fields of biomedical research.
Here are some research papers.
1. Sasaki M, et al. Soluble proteoglycan bikunin enhances neurogenesis in the subventricular zone of adult mice. Stem Cells. 2017;35(11):2244-2257.
2. Frobel J, et al. Soluble proteoglycans as modulators of mesenchymal stem cell differentiation. PLoS One. 2014;9(1):e85383.
3. Lee RH, et al. Soluble proteoglycan decorin promotes myogenic differentiation of human adipose-derived stem cells. Stem Cells Dev. 2011;20(4):631-639.
4. Midura RJ, et al. Hyaluronan regulates bone morphogenetic protein-7-dependent prevention and reversal of myofibroblast phenotype. J Biol Chem. 2016;291(22):11586-11599.
5. Vázquez FJ, et al. Therapeutic potential of chondroitin sulfate proteoglycans-based scaffold in tissue engineering for cartilage repair. Int J Mol Sci. 2019;20(20):5059.
6. Zhang Z, et al. Soluble biglycan promotes healing of full-thickness wounds in diabetic mice. Biochem Biophys Res Commun. 2016;479(4):815-820.
7. Santos NC, et al. Decorin expression is associated with a functional tumour suppressor profile in melanoma cells. Melanoma Res. 2008;18(3):184-195.
8. Xu J, et al. Soluble biglycan enhances BMP-2-induced osteogenesis by promoting the BMP-Smad signaling pathway. J Biol Chem. 2018;293(20):7949-7959.
9. Fiedler LR, et al. Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of α2β1 integrin activity. J Biol Chem. 2014;289(1):111-121.
10. Rühland C, et al. Soluble biglycan: a potential mediator in crosstalk between inflammation and regeneration. Sci Rep. 2016;6:30619.
11. Morin KT, et al. Soluble biglycan: a potential circulating biomarker of lung fibrosis and therapeutic target. BMC Pulm Med. 2021;21(1):146.
12. Cs-Szabó G, et al. Role of chondroitin sulfate (CS)–containing proteoglycans in human intervertebral disc degeneration. Int J Mol Sci. 2018;19(3):689.
13. Wang T, et al. Soluble biglycan as a new and independent predictive marker of clinically significant portal hypertension and esophageal varices in cirrhosis. PLoS One. 2015;10(11):e0142778.
14. Liu Y, et al. Chondroitin sulfate and hyaluronan regulate the self-renewal of B16 mouse melanoma cells by activating Erk1/2 via CD44 and syndecan-4. Cell Signal. 2015;27(5):943-956.
15. Wang T, et al. Soluble biglycan released from damaged fibrotic liver induces kidney tubular epithelial cell activation. J Biol Chem. 2017;292(19):7917-7929.