Objective: Feedback regulations of clock genes are associated with variety of cyclical phenomena such as a circadian rhythm. Recently, hair-cycle-dependent oscillations of clock gene expressions have been observed in mouse pelage follicles. In this study, we examined if such oscillations are involved in functions of the dermal papillae.
Methods: We used isolated vibrissa follicles to exclude the influence of non-follicular tissues on gene expression profiling. Vibrissa follicles were divided into 5 stages in anagen and 3 stages in catagen and were analyzed expression of clock genes by real-time RT-PCR for total RNAs that had been rapidly prepared from isolated vibrissa follicles or dermal papillae. In addition, the effect of CK1 inhibitor was examined on hair growth and gene expression profiling.
Results: Expression patterns of clock genes in whole follicles were classified into 3 categories. 1) Bmal1, Clock and Per2 had a peak of expression at proanagen and were down-regulated in catagen; 2) Cry1 and Rora were up-regulated at very early anagen through midanagen then down-regulated in catagen; 3) Rev-erba and Dbp had a peak of expression at very early anagen and greatly decreased their expression until early catagen. In the dermal papillae, most clock genes were down-regulated in anagen. However, Rev-erba showed an opposite pattern of expression, which had a peak of expression in early catagen. In addition, hair elongation of anagen hair follicles was suppressed by adding CK1 inhibitor IC261 in organ culture. Per2, Rora, Rev-erba, Hlf and Tef were down-regulated in them.
Conclusions: Vibrissa dermal papillae and whole follicles showed different expression patterns for some clock genes. These differences might reflect multiple roles of clock genes in the hair follicle system. Thus, the hair cycle progression might be controlled by clock genes and through CK1 activity in part, but its control mechanisms seem to be more complicated.