Fibulin

Fibulin is a family of extracellular matrix (ECM) and plasma proteins that play a crucial role in cellular structure and function. Fibulins are involved in various cellular processes such as cell adhesion, cell migration, and elastic fiber assembly. They are important for the structural integrity of connective tissues and have been implicated in several human diseases, including cancer, cardiovascular diseases, and inherited connective tissue disorders.

Structure and Function

Fibulins are characterized by a series of epidermal growth factor (EGF)-like repeats, which are calcium-binding motifs, and a unique C-terminal fibulin-type module. The family consists of several members, including Fibulin-1 through Fibulin-7, each encoded by a different gene and exhibiting distinct expression patterns and functions within the body.

Fibulin proteins interact with a wide range of other ECM proteins and components, such as elastin, fibrillin, and laminin, contributing to the assembly and stabilization of the extracellular matrix. Through these interactions, fibulins play a critical role in the formation of elastic fibers, which provide elasticity and resilience to tissues like skin, lungs, and blood vessels.

Clinical Significance

Alterations in fibulin expression or function have been associated with a variety of pathological conditions. For example, mutations in the genes encoding Fibulin-4 and Fibulin-5 have been linked to disorders affecting elastic tissues, such as cutis laxa, a condition characterized by loose, sagging skin, and systemic involvement including lung and vascular abnormalities.

In oncology, changes in fibulin levels have been observed in several types of cancer, where they can act either as tumor suppressors or promoters, depending on the context and specific fibulin member involved. The role of fibulins in cancer is complex, influencing tumor growth, invasion, and metastasis through modulation of the tumor microenvironment and interactions with cancer cells.

Research and Therapeutic Potential

Given their involvement in ECM organization and disease, fibulins represent potential targets for therapeutic intervention. Research is ongoing to better understand the mechanisms by which fibulins contribute to disease and to develop strategies for modulating their function in pathological conditions, including fibrosis, cancer, and inherited connective tissue disorders.

See Also

• Extracellular matrix
• Elastic fiber
• Cell adhesion
• Protein structure