Frontiers in Cell and Developmental Biology · 3 authors, 2 centres
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This narrative review summarizes the structure, expression, and functional roles of the extracellular matrix glycoprotein fibrillin-1 (FBN1). FBN1 mutations cause Marfan syndrome, and dysregulation of FBN1 is associated with cancers, cardiovascular disorders, and kidney diseases, with both depletion and overexpression paradoxically activating TGF-β signaling.
This narrative review describes fibrillin-1 (FBN1) as a large, cysteine-rich, calcium-binding extracellular matrix glycoprotein encoded by the FBN1 gene. Structurally, FBN1 contains multiple epidermal growth factor-like motifs and TGF-β binding modules, serving as a structural component of microfibrils in elastic and nonelastic connective tissue. FBN1 interacts with numerous microfibril-associated proteins, growth factors, and cell membrane receptors, mediating biological processes including cell survival, proliferation, migration, and differentiation. Mutations in FBN1 cause Marfan syndrome and a wide variety of genetic disorders with pleiotropic manifestations. Dysregulation of FBN1 expression is associated with the pathogenesis of cancers, cardiovascular disorders, and kidney diseases. A central paradox identified is that both depletion and overexpression of FBN1 upregulate TGF-β signaling via distinct mechanisms. The review notes that the role of dysregulated FBN1 in disease pathogenesis is just beginning to be unveiled and that future studies are needed to delineate context-dependent mechanisms.
