[P2-3-31] KLF5 expression in calcium-induced keratinocyte differentiation
Keywords:KLF5、細胞分化、発現制御
The maintenance of the balance of basal cell proliferation and differentiation is required for the squamous epithelial homeostasis. Krüppel-like factor (KLF) 5 directly regulates the proliferation-differentiation balance, but the association between KLF5 expression regulatory mechanism and cell differentiation remains largely unknown. KLF5 is considered to suppress the expression and function of differentiation-inducing factors, resulting in inhibits epithelial phenotype. CREB/ATF family is involved in the regulation of KLF5 gene expression. In this study, we examined KLF5 expression and the association between CREB-regulated KLF5 expression and differentiation in calcium-induced keratinocyte differentiation.
HaCaT cells, human keratinocyte cell line, were continued to be cultured in medium contained 0.03 mM (0.03 mM-Ca) or 0.15 mM calcium (0.15 mM-Ca), and then were induced terminal differentiation by calcium switch. In both 0.03 mM-Ca and 0.15 mM-Ca, endogenous KLF5 expression significantly increased after terminal differentiation. Endogenous CREB expression significantly increased after terminal differentiation in 0.03 mM-Ca but not 0.15 mM-Ca. Exogenous overexpression of CREB raised the level of KLF5 expression after terminal differentiation in 0.03 mM-Ca, but reduced in 0.15 mM-Ca. On the other hand, CREB knockout did not significantly alter KLF5 expression in terminally differentiated cells of both 0.03 mM-Ca and 0.15 mM-Ca.
These results suggest that CREB function may be reversed in 0.03 mM-Ca and 0.15 mM-Ca and the KLF5 expression regulatory mechanism by CREB can be altered in the process of calcium-induced keratinocyte differentiation.
HaCaT cells, human keratinocyte cell line, were continued to be cultured in medium contained 0.03 mM (0.03 mM-Ca) or 0.15 mM calcium (0.15 mM-Ca), and then were induced terminal differentiation by calcium switch. In both 0.03 mM-Ca and 0.15 mM-Ca, endogenous KLF5 expression significantly increased after terminal differentiation. Endogenous CREB expression significantly increased after terminal differentiation in 0.03 mM-Ca but not 0.15 mM-Ca. Exogenous overexpression of CREB raised the level of KLF5 expression after terminal differentiation in 0.03 mM-Ca, but reduced in 0.15 mM-Ca. On the other hand, CREB knockout did not significantly alter KLF5 expression in terminally differentiated cells of both 0.03 mM-Ca and 0.15 mM-Ca.
These results suggest that CREB function may be reversed in 0.03 mM-Ca and 0.15 mM-Ca and the KLF5 expression regulatory mechanism by CREB can be altered in the process of calcium-induced keratinocyte differentiation.