Transforming growth factor-beta-induced protein (TGFBI) (TGFBI)

Transforming growth factor-beta-induced protein (TGFBI), also known as BIGH3 or kerato-epithelin, is a 68 kDa extracellular matrix (ECM) protein that is highly induced by transforming growth factor-beta (TGF-beta) in various cell types [UniProtKB - Q15582]. It functions primarily as an adapter protein, facilitating cell-matrix interactions by binding to type I, II, and IV collagens as well as various integrins through its FAS1 domains and C-terminal RGD motif [Thapa et al., 2007, Int J Biochem Cell Biol]. TGFBI is critically involved in maintaining corneal transparency; mutations in the TGFBI gene are the primary cause of several autosomal dominant corneal dystrophies, such as Lattice and Granular types, where misfolded protein aggregates lead to visual impairment [Munier et al., 1997, Nat Genet]. Beyond the eye, TGFBI plays complex roles in cancer, where it can act as either a tumor promoter or suppressor by modulating cell adhesion, migration, and angiogenesis within the tumor microenvironment [Ween et al., 2012, Cancer Lett]. Current therapeutic development focuses on gene-silencing techniques like siRNA to reduce mutant protein expression in corneal diseases and the development of antibodies to target its pro-tumorigenic functions in specific cancers [Courtney et al., 2014, Gene Ther].

Other names

BIGH3Beta-ig-h3Kerato-epithelinRGD-CAPTGFBIp

Allele-specific silencing of mutant TGFBI mRNA via RNA interference (siRNA) to reduce the production of amyloidogenic or hyaline-forming proteins in the cornea; Neutralization of TGFBI protein or its interaction with integrins using monoclonal antibodies to inhibit tumor cell adhesion and migration.