Expression of hair keratins in the adult nail unit: an immunohistochemical analysis of the onychogenesis in the proximal nail fold, matrix and nail bed.

Abstract

Recently, the expression profiles of the members of the complex hair keratin family have been determined in the human anagen hair follicle. In contrast, the details of hair keratin expression in the human nail unit are poorly known. In order to fill this gap, we have performed an immunohistochemical study of the adult human nail unit by means of specific antibodies against nine hair keratins of both types (hHa2, hHb2, hHa5, hHb5, hHa1, hHb1, hHb6, hHa4 and hHa8) as well as three epithelial keratins (K5, K17 and K10). Formalin-fixed paraffin sections of adult nails were examined using monoclonal and polyclonal keratin antibodies, respectively. Longitudinal as well as transverse sections were investigated. Our study revealed two types of epithelial tissue compartments in the nail unit. The first comprised the eponychium and hyponychium and the nail bed, which expressed only epithelial keratins. While keratins K5, K17 (basal) and K10 (suprabasal) were found in the orthokeratinizing eponychium and hyponychium, throughout, the nail bed epithelium expressed only K5 and K17. The second type comprised the apical and ventral matrix which exhibited a mixed pattern of epithelial and hair keratin expression. Thus, K5 and K17 were expressed in the entire multilayered basal cell compartment of the apical and ventral matrix; however, in the latter, K5 and K17 also occurred in the lowermost layers of the overlying keratogenous zone. The hair matrix keratin hHb5, but not its type II partner hHa5, was seen in the entire keratogenous zone of the apical and ventral matrix, but was also located in the uppermost cell layers of the basal compartment of the ventral matrix, where it overlapped with K5 and K17. Similar to their sequential expression in the hair follicle cortex, hair keratins hHa1, hHb1, hHb6 and hHa4 were consecutively expressed in the keratogenous zone of both the ventral and, albeit less distinctly, apical matrix, with hHa1 initiating in the lowermost cell layers. The expression of hHa8 in only single cortex cells of the hair follicle was also preserved in cells of the keratogenous zone. In the region of the so-called dorsal matrix, we observed two histologically and histochemically distinct types of epithelia: (i) a dominant type, histologically similar to the eponychium and an associated K5, K17 and K10 keratin pattern which clearly extended into the apical matrix, and (ii) a minor type, histologically resembling the postulated dorsal matrix without a granular layer and a cuticle, and exhibiting extended K5 expression as well as hair keratin expression in superficial cells. The coexpression of hHb5 with K5 and K17 in the uppermost cell layers of the basal compartment and the lowermost layers of the keratogenous zone of the ventral matrix prompts us to designate this region the prekeratogenous zone of the ventral matrix. The two alternating types of histology and keratin expression in the dorsal matrix identify this region as a transitional zone between the eponychium and the apical matrix. Finally, our data clearly show that the ventral matrix is the main source of the nail plate. In addition, the mixed scenario of hair and epithelial keratins, including demonstrable amounts of K10, in superficial cells of the apical matrix, lends support to the notion that the dorsal portion of the nail is generated by the apical matrix.