Fibrillin is a large protein that makes up connective tissues throughout the body, providing structure and support. Its presence is fundamental to the overall structure and function of various bodily systems.
What Fibrillin Is
Fibrillin is a large glycoprotein secreted by fibroblasts into the extracellular matrix, an intricate lattice of proteins and other molecules surrounding cells. Within this matrix, fibrillin molecules connect to each other and to other proteins, forming thread-like microfibrils. These microfibrils are approximately 10-12 nanometers in diameter and have a periodic beaded appearance.
The primary gene for fibrillin is FBN1, located on chromosome 15. Fibrillin-1, encoded by the FBN1 gene, is the most abundant of the three known fibrillin isoforms in adult tissues. These microfibrils are components of elastic fibers, widely distributed in connective tissues like the skin, blood vessels, and ligaments.
Its Role in the Body
Fibrillin performs two main functions for maintaining body health and structure. It contributes to the structural support and elasticity of tissues, allowing them to stretch and recoil. This property is evident in the skin, where fibrillin helps maintain its flexibility and ability to return to its original shape after stretching. In blood vessels, particularly large arteries like the aorta, fibrillin microfibrils provide the necessary strength and flexibility to withstand the constant pulsatile flow of blood.
Fibrillin microfibrils also serve as a scaffold for elastin deposition, another protein that gives tissues their elastic properties. This combination is important in organs such as the lungs, enabling them to expand and contract during breathing. In the eyes, fibrillin is found in the suspensory ligaments of the lens, which help hold the lens in place and contribute to its ability to focus.
Fibrillin also regulates growth factors, such as transforming growth factor-beta (TGF-beta). Fibrillin microfibrils can bind to and store these growth factors within the extracellular matrix, controlling their availability and activity. This regulation is important for cellular processes, including cell growth, differentiation, and tissue repair. By influencing TGF-beta signaling, fibrillin helps maintain tissue homeostasis and contributes to proper tissue development and remodeling.
When Fibrillin Malfunctions
When fibrillin does not function correctly, it can lead to conditions affecting connective tissues throughout the body. The most recognized condition associated with fibrillin malfunction is Marfan syndrome, caused by mutations in the FBN1 gene. These mutations can result in reduced fibrillin-1 protein production or an altered protein structure, leading to weakened connective tissues.
Due to fibrillin’s widespread presence, Marfan syndrome can manifest with symptoms affecting multiple body systems. Skeletal abnormalities are common, including tall stature, long limbs, and flexible joints. Individuals may also experience chest wall deformities, such as a sternum that either protrudes or caves inward, and scoliosis, an abnormal curvature of the spine.
Cardiovascular problems are a concern in Marfan syndrome, as weakened connective tissue can affect the aorta, the large artery carrying blood from the heart. This can lead to aortic dilation or bulging (aneurysm), and potentially a tear in the aortic wall (dissection), which can be life-threatening. Eye issues are also observed, with lens dislocation (ectopia lentis) being a common feature where the eye’s lens shifts from its normal position. Other ocular problems may include myopia, glaucoma, and cataracts. Fibrillin malfunction impacts both structural integrity and signaling pathways, leading to a broad spectrum of clinical manifestations.