Retinoic acid delays keratinocyte senescence by suppression of betaig-h3 and p16 expression and induction of telomerase activity.
Retinoic acid (RA) plays an important role in the regulation of keratinocyte growth, differentiation, and senescence; however, the detailed mechanisms of RA regulation are still unclear. To investigate whether all-trans RA extends the in vitro lifespan of normal human epidermal keratinocytes (NHEKs) by affecting mitotic capacity and/or senescence, we studied the effects of all-trans RA on cell growth, senescence, the expression of betaig-h3 and Rb cell cycle regulators, and the telomerase activity of NHEKs after RA exposure. When primary NHEKs were cultured in medium containing 1 nM of all-trans RA, the proliferation and replicative senescence of the cells was significantly stimulated and inhibited, respectively, and the in vitro lifespan of the cells increased 1.4- to 1.5-fold compared to the vehicle control. The levels of betaig-h3 and p16 in 1 nM of RA-treated cells remained significantly lower than that of the vehicle control at all population doublings. All-trans RA also triggered induction of telomerase activity in NHEKs with increasing a population doublings induced by RA treatment. These results support that the ability of all-trans RA to postpone, but not prevent, senescence may be related to both partial inhibition of p16 and betaig-h3 expression and induction of telomerase activity.
Min
Byung-Moo
BM
Department of Oral Biochemistry, Seoul National University College of Dentistry, Seoul 110-749, Korea. bmmin@snu.ac.kr
Oh
Ju-Eun
JE
Choi
Chung-Mi
CM
D002455:Cell Division / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D000099222:betaIG-H3 Protein
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016326:Extracellular Matrix Proteins; D019098:Telomerase; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D000099222:betaIG-H3 Protein