**2. Fibulin-3 (Fb-3) gene expression**

Fb-3 also known as Epidermal Growth Factor (EGF) Containing Fibulin Extracellular Matrix Protein-1 (EFEMP1) is an extracellular glycoprotein generally expressed in most tissues already in their embryonic phase. It is one of the seven proteins that belong to fibulinic family. Fibulins are characterized by EGF-like domain-couple *calcium-binding-cb* layout (epidermal growth factor) and a C-terminal *fibulin type* module. Fb-3 is codified by the EFEMP1 gene (also known as S1–5) present in chromosome 2p16. EFEMP1 contains 11 exons and codifies for a protein of 493 aminoacids with a 55 kDa molecular mass [14].

#### **Figure 1.**

*Expression of Fb-3 in relation to the structures of the cellular matrix (by textbook of aging skin springer).*

*Fibulin-3 as a Biomarker of Pleuric Involvement by Exposure to Fibers DOI: http://dx.doi.org/10.5772/intechopen.104448*

The protein sequence contains a signaling peptide, five cbEGF domain couples preceded by a modified cbEGF domain and a *fibulin-type* C-terminal module. The modified cbEGF domain features an insert of 88 aminoacids. Under physiological conditions, Fb-3 is found in monomeric form. The recombining Fb-3 shows a small shaft-like structure with a globule at one of its ends, which probably consists of the cbEGF modified domain [15].

Fb-3, like many other molecules that form the base membrane, has preserved itself best among the several species, keeping 92–94% of aminoacids identical in human, rats, and mice. During growth process, Fb-3 is expressed at mesenchyme level, especially in bone and cartilage structures.

In studies on Fb-3, the EFEMP1 gene was originally cloned by senescent fibroblasts taken from a subject with Werner Syndrome, a disease characterized by early aging, where an EFEMP1 mRNA overexpression can be observed. However, no mutation or fault in the EFEMP1 gene has been associated with Werner Syndrome or any other aging factors [16].

In adults, Fb-3 is largely distributed in various tissues, including the eyes. Particularly, a high expression of this glycoprotein can be observed in epithelial and endothelial cells, in their base membrane (see **Figure 1**) [1].

The latter play an essential role not only in structural or filtering functions, such as kidney glomerules, but also because they come into play in determining cell polarity and regulating cellular metabolic, proliferation, differentiation, and migration processes.
