**2. Biological information of occludin**

There are four main types of intercellular connections in vertebrates: tight junctions, adhesion junctions, gap junctions, and desmosome junctions. Intercellular tight junctions, which can seal intercellular spaces, control hydronium, water, and other molecular pathways, and maintain cell polarity, as discovered by Farquhar and Palade [8]. Discovery of tight junctions revealed the complexity of cellular internal structural, and cellular tight junction proteins (cingulin [9], Zos [10], Tricellulin, JAM [10], and occludin [11]) further clarify the structural complexity and functional diversity of cells.

#### **2.1 Structure of occludin**

Occludin has four transmembrane segments, two extracellular loops (the first extracellular loop rich in tyrosine and glycine and the second extracellular loop rich in tyrosine) and two extracellular loops internal domains (NH2-terminal cytoplasmic domain and COOH-terminal cytoplasmic domain) (**Figure 1**). The main function of the COOH-terminal cytoplasmic domain of occludin is to mediate the basolateral transport and endocytosis of proteins, while occludin lacking the C-terminus can localize at tight junctions, the tight junctions cannot be assembled correctly and function is lost [12]. In addition, Bamforth et al. [13] found that occludin lacking or truncating the N-terminus of the extracellular domain can still target tight junctions and co-localize with ZO-1, but the function of tight junction barrier disappears, suggesting that the C- and N-terminal domains of occludin are involved in tight junction assembly and play a barrier function. In addition, the two extracellular loop domains of occludin are critical for the localization of cellular tight *The Role of Occludin in Vascular Endothelial Protection DOI: http://dx.doi.org/10.5772/intechopen.107479*

#### **Figure 1.**

*Structural insight into occludin. Occludin shares with general architecture as tetraspan transmembrane proteins colored in a gradient ranging from yellow at the N-terminus [N] to yellow at the C-terminus [C]. aa: Amino acid; G: Glycine; T: Tyrosine; EL1/2, extracellular loops 1 and 2; TM1 to 4, transmembrane domains 1 to 4.*

junctions. Occludin lacking the two extracellular loops is only present on the surface of basal cells but not cellular TJ [14].

#### **2.2 Tissue distribution and expression regulation of occludin**

Occludin is expressed in different cells and tissues with different expression level, and it is related to the function of tissues and organs. Occludin can be expressed in human, rat, mouse and other species, and it is mainly localized in arterial and venous vascular endothelial cells, blood-brain barrier, and blood-retinal barrier [14]. Although the expression of occludin could not be detected at the capillary-endothelial junction in mouse heart and skeletal muscle, occludin was highly expressed in brain capillaries [3], suggesting that occludin is essential for regulating the endothelial permeability of the blood-brain barrier. Morcos et al. [15] confirmed that under physiological conditions, occludin is highly expressed in retinal capillaries. However, in pathological conditions, the expression of occludin in the vascular endothelium will decrease significantly accompanied by different stress responses (inflammation, diabetes, cardiovascular diseases, neurodegenerative diseases, and atherosclerosis), and the permeability of vascular endothelium and the apoptosis of cell will increase [4], which suggests that occludin plays an important role in the blood-retinal barrier. In conclusion, under physiological and pathological conditions, the different expression levels of occludin in different tissues and cells are closely related to the tissue barrier properties.
