Aged mice overexpressing cellular repressor of E1A-stimulated genes 1 in adipose tissues exhibited increased liposarcoma incidence and shortened lifespan

Abstract

Cellular repressor of E1A-stimulated genes 1 (CREG1) is a multifunctional secreted glycoprotein that regulates p16-dependent cellular senescence and cell differentiation and accelerates brown adipogenesis. We recently demonstrated that the CREG1 levels in serum, liver, and kidney were significantly increased in aged wild-type (WT) mice, where age-related renal impairment was further aggravated by promoting cellular senescence. Based on these findings, we hypothesized that the constitutive regulation of CREG1 expression in vivo may affect lifespan. In this study, we revealed that the average lifespan of adipocyte P2-CREG1 transgenic (Tg) mice was shorter than that of WT mice. Moreover, we determined that this reduced lifespan was associated with an increased incidence of liposarcoma (LPS). Our findings indicated that the development of LPS in Tg mice may be driven by chronic inflammation induced by the p19^Arf-mouse double minute 2 pathway in white adipose tissue (WAT). These findings indicate that long-term alterations in CREG1 expression in vivo may affect tumor development in the WAT.