Ultraviolet B irradiation up‐regulates MM1 and induces photoageing of the epidermis.

Background: ΔNp63α and c‐Myc are key transcription factors controlling proliferation and senescence in epithelial cells. We previously reported that the c‐Myc modulator MM1 and its E3 ligase, HERC3, together with the transcription factor ΔNp63α, compose a feedback loop, which regulates proliferative senescence in MCF‐10A mammary epithelial cells. However, it is unknown whether this loop is involved in skin ageing. On the other hand, ultraviolet B (UVB) rays are assumed to be the main culprits for photoageing of the epidermis, but the underlying mechanisms are obscure. Aims: To investigate whether MM1/ΔNp63α axis is involved in UVB‐induced photoageing of the epidermis. Materials and Methods: HaCaT human immortalized keratinocytes overexpressed with MM1, knocked down with c‐Myc or irradiated with UVB, were subjected to MTT assays to measure cell proliferation, as well as RT‐qPCR or immunoblot to detect the members of MM1/ΔNp63α loop and the cellular senescence markers. Meanwhile, primary normal human keratinocytes (NHKs) or mice were irradiated with UVB, followed by immunoblot analysis, SA‐β‐gal, haematoxylin‐eosin or immunohistochemistry staining. Results: Overexpression of MM1 down‐regulated ΔNp63α and induced proliferative senescence in the HaCaT cells. In the HaCaT cells, NHKs and the mouse epidermis, UVB irradiation increased MM1 mRNA level and led to a down‐regulation of ΔNp63α, HERC3 and c‐Myc, concomitant with cellular senescence or photoageing. Additionally, knock‐down of c‐Myc induced proliferative senescence in the HaCaT cells and abrogated UVB‐induced cellular senescence. Conclusions: UVB up‐regulates MM1 and consequently modulates ΔNp63α and c‐Myc, which may account for the proliferative senescence of keratinocytes and photoageing of the epidermis. [ABSTRACT FROM AUTHOR]