This article shows a link between collagen production and energy problems associated with Metabolic Diseases. Could this be a new avenue of research?
Defining the cellular sources of collagens in the normal and diseased states of the above metabolic tissues is thus critical to understanding metabolic disease. Under certain pathological conditions, the excess accumulation or collapse of collagens may disrupt normal cell-cell interactions, and cause the loss of tissue compliance or elasticity.
Finally, these disruptions of collagens result in tissue dysfunction such as atherosclerosis of the blood vessels, pulmonary fibrosis, liver cirrhosis and fibrosis in other organs.
This review will focus on the role of collagens in metabolic tissues, and attempt to summarize the function of collagens in energy metabolism.
For a more general overview of collagen and its functions, see reference page:
Connective Tissue and Collagen Basics
The main components of the interstitial matrix and the basement membrane in the extracellular region of animal tissue are referred to as the extracellular matrix (ECM). The ECM plays important roles in providing support and anchorage for cells, regulating intercellular communication, and storing a wide range of cellular growth factors . Thus, the rapid and local growth factor-mediated activation of cellular functions are triggered by changes in physiological conditions, without de novo synthesis
The ECM is tissue specific in quality and quantity. Components of the ECM are secreted from the intracellular region of resident cells via exocytosis. The main components of ECM are the interlocking mesh of fibrous proteins and glycosaminoglycans (GAGs). Furthermore, the main fibrous proteins are collagens, of which 29 types have been reported . The functions of these proteins include protection and support, and forming connective tissue, tendons, bone matrices, and muscle fiber.
Collagen proteins are large and complex, with multiple distinct domains, and are highly conserved among different species. Almost all collagen proteins are glycoproteins, protein cores made in the rough endoplasmic reticulum, and posttranslationally modified by glycosyltransferases in the Golgi apparatus. After being secreted into the ECM as precursors via exocytosis, they need a complex processes such as the cleavage of N- and/or C-propeptides which occurs via highly specific proteinases and then become mature collagens
Skeleton muscle and tendon
The ECM in skeletal muscle is organized in different levels, and collagens are the most abundant structural components of skeletal muscle ECM. 1% to 2% of muscle tissue and 6% of the weight of muscles are collagens
In tendons, the tendonosis occurs when the fibrous material collagens in a tendon begins to degenerate. This may occur as the result of injury. The tendon becomes tangled, weak and jelly-like when collagen degenerates. Additionally, muscular dystrophies are also associated with changes in matrix
Collagens play critical roles in force transmission and tissue structure maintenance in tendons, bone and muscle. It is well known that the contractile filaments in skeletal muscle are important to force development, and the tendon tissue transform this developed force from the muscle to the bone. In addition, collagens also play a role in the skeleton muscle development.
Smooth muscle cells and cardiac muscle cells
Vascular smooth muscle cells (VSMCs) normally reside in the media of the artery, lined with endothelial cells, and are surrounded by a specialized thin sheet-like structure of extracellular matrix components, including collagen types I, III, IV and V et al
Production of a functional matrix in SMCs requires the coordinated expression, modification, process of the ECM proteins, and some others signals such as PDGFÃŸ, EDG1 and TGF-ÃŸ that are involved in the processing and assembly of most ECM networks, including basement membranes, elastic fibers, and large proteoglycan matrices.
Additionally, the roles of collagens in heart, especially in the heart remodeling, have attracted enormous attention recently. The components of cardiac ECM are composed of fibrous proteins and glycosaminoglycans (GAGs). Fibrous proteins such as collagen and elastin serve as reinforcements for the myocardium. GAGs such as glycoproteins and proteoglycans function as the space-filling concrete in the heart.
The mechanical support for pumping blood in the heart is also provided by Collagens
A number of muscle and related pathologies involve changes in matrix properties
This is the first hint I’ve seen linking EDS muscle problems/pain to collagen production in the ECM.
Cell signal pathway
This is where things get interesting:
The diverse array of collagens not only provide the physical structure of the cell, but also various biological functions largely through them to bind many other interacting partners such as growth factors, other ECM proteins, signal receptors, and adhesion molecules like integtrins.
The collagens perform profound effects on cell fate and behaviors via interacting with the surface receptors and growth factors and then transduce to cytoplasmic signal pathways
The collagens can collaborate with their receptor integrins, growth factor receptors and intracellular signals to regulate gene expression associated with metabolic cell growth, differentiation, survival and glucose uptake
Metabolic diseases continue to be a major health challenge of pandemic proportion in the world. They can be caused by lifestyle or genetic variants, leading to the dysfunction of energy balance through a complex pathophysiological process. The ECM remodeling and tissue destruction are required during these complex process. Lots of component increases, decreases or modifications are involved in ECM remodeling, especially collagens remodeling. With the current level of research and increasing understanding of the function of collagens, there is hope that better medications will emerge to control complex metabolic diseases.
It is well-known that extracelluar signals including growth factors and cytokines bind to specific receptors on the surface of their target cells. Recently, more and more findings were reported that collagen not only builds the main structural components among the cells, but also covalently anchors to the plasma membrane of the cells to enhance the efficient binding between the cytokines and their specific receptors, thereby modulating their mitogenic and angiogenic effects on different types of cells
The newly recognized importance of collagen may finally stimulate more research into connective tissues of all kinds, and the production defects caused by EDS.
Additionally, the recent discovery of additional functions of collagen, not just as a support structure, but an active agent of changes in other kinds of cells may finally provide an explanation of more of the stranger symptoms of EDS.
Obviously, the ECM components, especially the collagens, will be recognized as the key regulators in cell physiological activities in future.
On her blog, http://strengthflexibilityhealtheds.com/, Kendra continues where this article leaves off, and gives a better explanation of the interrelationships and consequences when things go awry: