Revista nº 813

Artificial oral mucosa | Ibáñez Cortés M, et al. Actual Med. 2021; 106(813): 177- 187 180 3. Specialized mucosa: in the case of mucosa with taste function, specially in dorsal tongue and taste papillae, a parakeratinizated epithelium is found. For mucosa with defensive function, specially in lingual tonsil, a non-keratinizated epithelium can be identify. Both types of specialized mucosas present connective tissue and submucosa. Several works have used different histological techniques to identify tissue structure, cellular components and the extracellular matrix of native human oral mucosa. Most of the publications use rutinary hematoxylin and eosine for the visualization of acidophil and basophilic components (20). In addition, histological features for native human oral mucosas are also investigated by using immunohistology and histochemical techniques. In the present review, we pretend to highlight the most relevant findings of current histological studies regarding the epithelium, basal membrane, connective tissue and submucosa of the native human oral mucosa. EPITHELIAL TISSUE For histological study of the epithelium of the native human oral mucosa the most used histological technique is the immunohistochemistry to detect key epithelium-related proteins, cytokeratins (CKs). In this milieu, CKs are a cytoskeletal protein family of intermediated size synthesized by epithelial cells classically divided in type I or acidic proteins (CK 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 and others) and type II or basic proteins (CK 1, 2, 3, 4, 5, 6, 7, 8) (21). Most of the scientific publications associate the expression of CKs 5-14 and 17 to the basal layer cells. The CKs 4-13, and 6-16 expression to the suprabasal layers and CKs 3-12 and 10 are linked to the most superficial epithelial layers of the keratinized oral mucosa (10,22-24) (Table 2). Different authors classify some CKs as specific of keratinized or nonkeratinized epithelia. However, this affirmation is not correct at all because of these CKs also can be found in the opposed epithelia. For example, Winning et al classified CKs 6-16 as specific proteins of keratinized epithelia but they are also found in nonkeratinized epithelium as mouth’s floor and ventral tongue (10, 15, 24). Several authors have used CKs as epithelial markers in the different types of oral mucosa (masticatory, lining, and specialized mucosa) (Table 1). First, for masticatory mucosa as gingiva showed possitive expression of CKs 1, 2, 4, 5, 6, 8, 10, 11, 13, 14, 16, 17, 18 and 19 (10,25). In the case of masticatory mucosa as hard palate CKs 1, 6, 10, 16 and 76 were possitively expressed (10,22,23,26). Secondly, in the case of lining mucosa as mouth’s floor and ventral tongue CKs 4, 5, 6, 13, 14, 16 were found. However, CK 19 expression was exclusively found in mouth´s floor (24). In contrast, lips and soft palate were substatially different. In the case of lips CKs 1, 4, 5, 13, 14 were expressed (12) and for soft palate CKs 7, 8, 18 and 19 were also positive (10). Furthermore, for lining mucosa as cheeks an epithelia pattern based on CKs expression was not found. Finally, in areas with specialized mucosa as dorsal tongue and lingual tonsil a common CKs expression was found (CKs 5, 6, 13, 14) being CKs 1, 2, 4, 15, 16 and 17 exclusive for dorsal tongue. In the same way, CK 7 was unique for lingual tonsil (27,28). Different types of taste papillae are located along the tongue expressing on the top CKs 1, 2, 4, 10, 11, 13, 16. Strinkingly, taste buds situated on the side of papillae show a high expression of CKs 8, 18, 19 similar to simple epithelium (28). Another proteins involve in oral mucosa epithelial differentiation are filaggrin, involucrin and loricrin. According to this, filaggrin and involucrin were expressed in masticatory and specialized keratinized oral mucosa. Nonetheless, in non-keratinized epithelium as lining mucosa and lingual tonsil of specialized oral mucosa, filaggrin and involucrin proteins were absent (22,24) (Table 2). Apart from the use of CKs as key epithelial markers, few authors have also used immunohistochemical techniques to detect another epithelial markers, usefull for the characterization of oral mucosa epithelium including CD44 (a cell-cell adhesion marker), desmoglein, desmoplakin, desmokollin (desmosomes associated proteins), connexin-26 and 43 and α4-β6 integrins (junction of epithelial and connective tissue) that were expressed in all types of oral mucosa (5,12,15) (Table 2). BASEMENT MEMBRANE Histological characterization of basement membrane is based on immunohistochemical and histochemical techniques due to the amount of proteins of different nature. As we mentioned before, basement membrane is composed by basal lamina and reticular lamina. In this regard, few studies have reported the presence of BP 180, BP 230, ladinin, laminin-5, entactin, fibronectin and collagen IV as markers of basal lamina. In terms of reticular lamina, the literature have addressed the expression of collagen III and VII (15,29) (Table 3). All these markers play an important role in native human oral mucosa differentiation and characterization. Furthermore, histochemical techniques have detected glycoproteins of basement membrane using periodic acid-Schiff staining (11, 30). Moreover, for the reticular lamina characterization, Gomori’s technique has been used to detect reticulin fibers formed by trimeric collagen type III (19,30) (Table 4). CURRENT H I STOLOGY F I ND I NGS I N NAT I VE HUMAN ORAL MUCOSA