Hedgehog Signaling, Keratin 6 Induction, and Sebaceous Gland Morphogenesis

The study investigated the immunostaining patterns of 10 anticytokeratin antibodies in trichoblastic fibroma, trichoepithelioma, and basal cell carcinoma (BCC), comparing them with normal skin. It found that trichoblastic fibroma and BCC shared similar cytokeratin expression patterns, making them indistinguishable by these markers alone. However, the presence of CK7 in trichoblastic fibroma and BCC, but not in trichoepithelioma, suggested that trichoblastic fibroma and BCC might retain fetal phenotypic characteristics, differentiating them from trichoepithelioma. This supported the idea that trichoepithelioma and trichoblastic fibroma are distinct entities, despite being previously considered a single tumor group. The study included 3 cases of trichoblastic fibroma, 7 cases of trichoepithelioma, and 29 cases of BCC.

The study investigated the expression of keratin 17 (K17) during mouse skin development, revealing that K17 synthesis began in embryonic day 10.5 in a subset of epithelial cells. These cells later formed placodes, precursors to ectoderm-derived appendages like hair, glands, and teeth. The spatial distribution of K17 corresponded with lymphoid-enhancer factor (lef-1), a protein involved in epithelial–mesenchymal interactions. Ectopic expression of lef-1 in adult transgenic mice induced K17, suggesting a link between K17 expression, skin morphogenesis, and wound repair. This research highlighted the role of K17 in skin development and its potential involvement in epithelial lineage definition.

The study identified that mutations in the keratin 17 (K17) gene were responsible for both pachyonychia congenita type 2 (PC-2) and steatocystoma multiplex, with the phenotypic outcome being independent of the specific mutation. Three unrelated families with K17 mutations were examined, revealing that two families shared the same missense mutation (R94C) but exhibited different phenotypes: one with classical PC-2 features and the other with steatocystoma multiplex. A third family with PC-2 had a different mutation (N92S). The research highlighted that K17 mutations were a common underlying cause for both conditions, expanding the known distinct mutations in K17 to 11.

The study investigated the regulatory sequences of the human keratin 6a (K6a) gene responsible for inducible expression in stratified epithelia following injury. Using transgenic mice, researchers found that the proximal 960 base pairs of the 5'-upstream sequence of the K6a gene were sufficient to induce beta-galactosidase expression in response to epidermal injury and chemical treatments known to induce K6 expression. The critical regulatory sequences for this inducibility were located between -960 and -550 base pairs, with enhancer elements influencing activity found between -2500 and -5200 base pairs. These findings highlighted the specific genetic elements involved in the gene expression response to epithelial injury.

The study analyzed the keratin expression in 15 cases of basal cell carcinoma using immunohistochemistry. It found that the tumors strongly expressed primary keratins 5 and 14, typical of basal keratinocytes, but did not express secondary keratins 1 and 10, which are associated with skin differentiation. Keratin 17, linked to the outer hair root sheath, was consistently expressed in all tumors, while keratin 19, normally found in parts of the hair follicle, was present in four cases. Keratin 16, associated with high cell turnover, was often induced in the overlying epidermis but was rare in the tumor tissue. Simple epithelial keratins 8 and 18 were not expressed. The keratin profile of the tumor cells resembled that of basal cells in the hair root sheath, supporting the hypothesis of a follicular origin for basal cell carcinomas, but also suggested a potential origin from interfollicular pluripotent stem cells differentiating towards follicular structures.