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The hard-keratin-containing portion of the murine hair shaft displays a positive immunoreactivity with an antibody against the soft epithelial keratin, K17. The K17-expressing cell population is located in the medulla compartment of the hair. Consistent with this observation, K17-containing cells also occur in the presumptive medulla precursor cells located in the hair follicle matrix. Western blot analysis of hair extracts prepared from a number of mouse strains confirms this observation and suggests that K17 expression in the hair shaft is a general trait in this species. The expression of K17 in human hair extracts is restricted to eyebrow and facial hair samples. These are the major sites for the occurrence of the pili torti (twisted hair) phenotype in the type 2 (Jackson-Lawler) form of pachyonychia congenita, previously shown to arise from inherited K17 mutations. Given that all forms of pachyonychia congenita show an involvement of the nail, we compared the expression of the two other genes mutated in pachyonychia congenita diseases, K6 and K16, with that of K17 in human nail. All three keratins are abundantly expressed within the nail bed epithelium, whereas K17 protein is expressed in the nail matrix, which contains the epithelial cell precursors for the nail plate. Our data suggest a role for K17 in the formation and maintenance of various skin appendages and directly support the concept that pachyonychia congenita is a disease of the nail bed.

The behavior of the keratinocyte during the initial stages of cutaneous wound repair has been the subject of intense investigation. Most of these studies have focused on the lateral edges of wounds as the source of activated keratinocytes. Less attention has been directed towards elucidating the role of the appendageal structures as sources of keratinocytes for re-epithelialization, particularly the sweat apparatus. Surgical wounds of specific depths were created in pig skin, above and below hair follicles, and wound healing was allowed to take place in a setting in which lateral ingrowth of keratinocytes by migration was prevented. In this manner, all re-epithelialization occurred from residual appendageal structures. In those wounds where only sweat gland elements remained, an epithelium formed that had clinical, morphologic, and protein electrophoretic features closer to palmar/plantar or mucosal-like epithelia. In contrast, wounds that retained elements of the hair follicle healed faster and the resultant epithelium clinically, morphologically, and biochemically resembled the surrounding nonwounded epidermis. These findings establish that the sweat apparatus is capable of re-epithelializing the skin surface after a major cutaneous wound, but may not be capable of mimicking the epidermis.

Keratins are the major structural proteins of the epidermis. Analyzing keratin gene sequences, appreciating the switch in keratin gene expression that takes place as epidermal cells commit to terminally differentiate, and elucidating how keratins assemble into 10-nm filaments have provided the foundation that has led to the discoveries of the genetic bases of two major classes of human skin diseases. In this report, we review the cell biology and human genetics of these diseases, epidermolysis bullosa simplex and epidermolytic hyperkeratosis. Both of these diseases are epidermal disorders of keratin, typified by cell fragility as a consequence of defects in the mechanical strength of basal epidermolysis bullosa simplex or suprabasal epidermolytic hyperkeratosis cells.