Changes in Expression of Apoptosis-Associated Genes in Skin Mark Early Catagen

Abstract

Programmed cell death is central to hair biology, as the hair follicle undergoes cycles of growth (anagen), regression (catagen), and rest (telogen). During catagen, the hair follicle shortens via a pathway of programmed cell death and apoptosis. The molecular mechanisms involved in this process have not been elucidated yet. Using reverse transcriptase-polymerase chain reaction, we examined in this study the expression in total skin, throughout one hair cycle, of a series of regulatory genes associated with apoptosis. We show that gene expression within skin is hair-cycle-dependent. Transforming growth factor-beta was expressed immediately before catagen; therefore, it might be involved in the early signaling of this process. Tumor necrosis factor-beta was expressed during catagen and might be involved in follicular apoptosis. Several proto-oncogenes and transcription factors have been described in the regulation of apoptosis in other systems. Here we show that the transcript levels of c-myc, c-myb, and c-jun changed immediately before or during early catagen and thus could be involved in the signaling or regulation of catagen. Levels of p53 remained constant throughout anagen and catagen, suggesting that p53 is not involved in the developmentally induced apoptosis of the hair follicle. The variable expression throughout the hair cycle of the genes described demonstrates the dynamic changes of the skin and underscores the importance of studying the complete hair cycle when characterizing any molecule in skin.

Visualization of Lymphotoxin-β and Lymphotoxin-β Receptor Expression in Mouse Embryos

“…LT␤R is also expressed in the thymus at this time even though a role for the LT system in thymic development or function has not been revealed in genetically deleted mice (34). The embryonic expression of LT␤ in the skin is intriguing given reports of nonlymphoid expression of LT␣ RNA or protein in inflamed epithelial layers such as in lichenoid skin, in keratinocytes from the middle ear with the hyperproliferating disease cholesteatoma, in skin following hair regression, and in melanocytes (35)(36)(37)(38). The expression of LT␣ or LT␤ in nonlymphoid/myeloid cells at sites of inflammation has not been extensively studied.…”

Diverse developing mouse lineages exhibit high-level c-Myb expression in immature cells and loss of expression upon differentiation

“…Matrix cells at this stage are just basal to high-level keratin expression, and suggests that c-myb expression can serve as a molecular marker for cells that are undergoing a commitment to di erentiation program that gives rise to the hair follicle inner root sheath. A previous detection of c-Myb expression in hair follicles by RT ± PCR techniques (Seiberg et al, 1995) was not able to distinguish variations according to hair follicle growth cycle or to speci®c cell types and growth stages.…”

“…c-Myb was not expressed in catagen or telogen stage hair follicles. Hair follicles have been previously reported to express c-myb through RT ± PCR analyses of RNA from shaved mouse skin (Seiberg et al, 1995), but the stage or cell type speci®city was unable to be addressed nor the potential contribution be discerned of c-myb expression by activated T cells or melanocytes (Gewirtz et al, 1989;Hijiya et al, 1994). During anagen, we hypothesize that c-Myb could be serving to both suppress the terminal di erentiation of inner and outer root sheath cells derived from the follicular matrix cells (Zhou et al, 1995), and regulate speci®c gene expression in the immature matrix cells.…”

Clusterin expression within skin correlates with hair growth

“…It is important to emphasize that these data represent the expression pattern of total skin. Correlations to hair cycle should not be confused with expression within the hair follicle itself, since many cell types within skin could contribute to a cycle dependent expression pattern (see Seiberg et al, 1995, and references therein).…”