Myofibroblasts: Structure, Function & Diseases

Myofibroblasts are a special type of connective tissue cell. They play an important role in physiological processes, but can also be involved in pathological processes.

What are myofibroblasts?

Myofibroblasts are special cells that are an intermediate form of connective tissue cells (fibroblasts) and smooth muscle cells. Myo comes from Greek and is a part of speech meaning muscle. This partial name recognizes the fact that myofibroblasts contain contractile elements that give them properties similar to those of smooth muscle cells. They have the capacity for prolonged contractions (tensions) that are involuntary. Fibroblasts are cells that, when active, are responsible for building connective tissue. They produce collagen fibers and molecular components of ground substance in the extracellular space. Myofibroblasts are capable of generating large amounts of collagen when stimulated to do so by appropriate factors. They are found in various tissues in which they perform different functions. Accordingly, their formation and differentiation is possible in different ways. They can arise from embryonic stem cells by direct differentiation, from smooth muscle cells, or from certain connective tissue cells in capillary walls (pericytes). Most commonly, however, they arise from fibroblasts that are not yet fully differentiated in the presence of specific growth factors and signaling cells in the tissue.

Anatomy and structure

The cells of myofibroblasts are divided into two parts by their functional structure. The connective tissue portion contains much rough endoplasmic reticulum, where a large amount of type III collagen can be produced. This represents a precursor of type I collagen, which is responsible for the structure and regulated fibrous structure in intact connective tissue. The large Golgi apparatus forms the membranes necessary for the construction of the channel system through which the collagen components are transported to their site of action. The second part of the myofibroblast cells has an actin-myosin complex, which corresponds to that in smooth muscle cells. Actin and myosin are protein strands that are coupled together in such a way that they can contract (contract) in response to an adequate stimulus and with the expenditure of energy. Unlike skeletal muscle, smooth muscle cells are not striated and cannot contract as quickly. On the other hand, they are able to maintain strong tension for a long time. A special feature of myofibroblasts is their direct connection with fibronectin filaments in the extracellular matrix. These protein chains form a bridge system with which the cells are interconnected. The connection allows contraction to be transmitted to the entire system and thus to larger tissue structures.

Function and tasks

Myofibroblasts are found in the subcutaneous layer of almost all mucous membranes. There they are responsible for the maintenance of tension and the physiognomy of specific tissue forms. The formation of crypts (retractions) and protrusions in the small intestine is largely determined by their contractility. The maintenance of tension and volume in vessels is also one of their functions, for example in the tubules of the testis and the capillaries. These fine tubes, unlike the large arterial blood vessels, do not contain a muscular layer of smooth muscle cells. However, due to the presence of myofibroblasts, a residual function is present to adjust the tension of the vessel walls to meet various demands. Perhaps the most important function of myofibroblasts is their involvement in wound healing. The body attempts to close tissue defects caused by injury or other pathological processes as quickly as possible. Myofibroblasts play an important role in this process. The immune defense is significantly involved when tissue damage occurs. Among other things, more macrophages (scavenger cells) are sent to the damaged area to take up and phagocytose dead tissue particles. The appearance of these cells represents the initial stimulus for the conversion of fibroblasts to myofibroblasts. These produce large quantities of collagen fibers, which are laid over the defective area like a net and form a temporary wound closure. At the same time, they are connected to each other and to the wound edges via fibronectin filaments.The contraction of all myofibroblasts causes them to be pulled together, an important process for accelerating wound closure. In further steps, this reticular structure is remodeled. The type III collagen becomes type I, and the fibers arrange themselves along the direction of traction. The myofibroblasts become inactive and cease their tensile activity.

Diseases

The action capacity of myofibroblasts is basically constitutional and decreases with age. Connective tissue weaknesses are largely determined by these specifications and developments. Regular physical activity cannot completely stop or reverse this process, but it can have a positive influence on its course in the long term. The occurrence of myofibroblasts depends on mediators that initiate their differentiation. If these are absent or present only in low numbers, not enough cells are converted. They cannot or cannot sufficiently fulfill the functions they normally perform. Weaknesses of the immune system in particular can have such consequences, but so can genetic defects affecting the growth factors that are important for differentiation. Increased myofibroblast activity may in turn be involved in pathological processes called fibrosis. These are diseases in which there is a strengthening of the connective tissue framework of organs. They are usually caused by the absorption of toxins over a long period of time or by autoimmune diseases. As a result, in the course of the disease process, the stretching capacity of the connective tissue is significantly reduced and the functioning of the affected organs is considerably impaired. Typical examples of diseases caused by toxins are pulmonary fibrosis resulting from increased exposure to coal dust, asbestos or flour dust. Scleroderma is an autoimmune disease in which the skin and fascia are affected by remodeling of the connective tissue. Often, the significant reduction in lung function due to the involvement of the pulmonary fascia is the reason for the limited lifespan.