| 内容提要: |
to anticipate daily environmental changes, most organisms developed endogenous timing systems, the so-called circadian (~24 hours) clocks. Circadian rhythm are reflected in all cells of the body and meet environmental challenges associated with the solar day. Our skin is directly exposure to the environment, and forms the barrier between the body and environment, protect us against major environmental stresses, including UVB, Heat, Chemical injury and Physical injury. So it is not surprising that it is profoundly subjected to time-of-day-dependent changes in the environmental conditions, such as exposure to UV irradiation.
At a cellular level, the circadian clock mechanism is composed of interdependent feedback loops of transcription and translation of specific gene products, as shown in this picture: Clock and Bmal1form a preliminary heterodimer, binds to E-box motif in the promoter region or clock controlled genes.This binding leads to PER and CRY transcription and then PER and CRY form a second heterodimer, which prevents the first heterodimer formation and thereby inhibits their own transcription. This cycle leads to approximately 24h oscillatory rhythm.
Above all, in human keratinocytes, UVB induced apoptosis and pro-inflammation is Bmal1/Clock dependent circadian ryhthm behavior. Apoptosis is P53 dependent, and Pro-inflammation is NF-kappaB mediated.
And this topic can Insights in the circadian regulation of physiological processes crucial for UVB-induced apoptosis and inflammatory response in human keratinocytes. And Lead to optimized drug delivery and sophisticated treatment for skin diseases related to rhythm variation, such as cutaneous pruritus and atopic dermatitis. |