Biochemical Changes in the Infundibulum During Comedogenesis
The process of comedogenesis is thought to be due to hyperproliferation of ductal keratinocytes, inadequate separation of the ductal corneocytes, or a combination of both factors, resulting in microcomedones. Hyperproliferation of basal keratino-cytes in acne has been demonstrated (180,181) and correlates with keratin 16 expression, a marker for hyperproliferation suprabasally (182). Aldana et al. (183) proposed a cycling of normal follicles through different levels of expression of Ki-67 (a proliferation marker) and keratin 16 and that these represent different stages of development of the microcomedone. The point at which both Ki-67 and keratin 16 are coexpressed by the follicle is when the follicle is susceptible to comedogenic changes (184).
A more extensive investigation of adhesion in follicles is required. In epidermis, intercellular adhesion is mediated by lipids, cellular adhesion molecules, and desmosomes. At the present time, the relative importance of follicular intercellular lipids in normal and acne follicles is unclear due to the experimental difficulties encountered obtaining sufficient material for analysis. Hypercornification from the retention of desmosomes was described to be a contributory factor to the formation of acne lesions. However, no differences were detected between staining for these epitopes in the wall of normal and comedonal follicles (29).
Although it is clear that we now know a great deal about the pilosebaceous unit at the structural, biochemical, and physiological levels, there are still considerable gaps in our understanding. Much of the early work was descriptive biology of the structure obtained using immunohistochemical studies. Over the last decade, several in vitro models systems (isolated organ culture, cultured sebocytes) have made it easier to study the cellular processes in the follicle, including sebum production and the effect of inhibitors and stimulators. There is also now a good deal of information about the chemistry and biosynthesis of sebum components, and we also have a much better understanding of the cell biology of the pilosebac-eous duct. Even so, we are still unable to precisely define the cause of one of the most common skin diseases, namely acne, which affects a very large proportion of the population globally.
The author wishes to acknowledge and thank Professor W Cunliffe for kindly allowing the use of Figure 1B, and the journal "Retinoids and Lipid Soluble Vitamins in Clinical Practice" for kindly allowing the use of Figures 1A, 2, and 3.
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