Masashi Yoshida

Bio: Masashi Yoshida is an academic researcher from Chiba University. The author has contributed to research in topics: Frizzled & Insulin receptor. The author has an hindex of 3, co-authored 3 publications receiving 368 citations.

IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis

Abstract: Insulin-like growth-factor-binding proteins (IGFBPs) modulate the actions of insulin-like growth factors (IGFs) but they also have functions independent of IGFs This study reports a new function for IGFBP-4 as a cardiogenic growth factor, showing that IGFBP-4 enhances cardiomyocyte differentiation in vitro, and knockdown of IGFBP-4 attenuated cardiomyogenesis both in vitro and in vivo The effect was independent of IGF binding, and was mediated by canonical Wnt signalling IGFBP-4 physically interacted with a Wnt receptor Frizzled 8 (Frz8) and a Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited Wnt3A binding to Frz8 and LRP6 This paper provides the first molecular link between IGF signalling and Wnt signalling The research could thus pave the way towards understanding how anomalies in this process give rise to congenital heart defects and could potentially yield new strategies to repair tissue damaged by heart attacks This study reports a function for IGFBP-4 as a cardiogenic growth factor, showing that IGFBP-4 enhances cardiomyocyte differentiation in vitro, and knockdown of IGFBP-4 attenuated cardiomyogenesis both in vitro and in vivo The effect was independent of IGF binding, and was mediated by canonical Wnt signalling IGFBP-4 physically interacted with a Wnt receptor Frizzled 8 (Frz8) and a Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited Wnt3A binding to Frz8 and LRP6 Insulin-like growth-factor-binding proteins (IGFBPs) bind to and modulate the actions of insulin-like growth factors (IGFs)1 Although some of the actions of IGFBPs have been reported to be independent of IGFs, the precise mechanisms of IGF-independent actions of IGFBPs are largely unknown1,2 Here we report a previously unknown function for IGFBP-4 as a cardiogenic growth factor IGFBP-4 enhanced cardiomyocyte differentiation in vitro, and knockdown of Igfbp4 attenuated cardiomyogenesis both in vitro and in vivo The cardiogenic effect of IGFBP-4 was independent of its IGF-binding activity but was mediated by the inhibitory effect on canonical Wnt signalling IGFBP-4 physically interacted with a Wnt receptor, Frizzled 8 (Frz8), and a Wnt co-receptor, low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited the binding of Wnt3A to Frz8 and LRP6 Although IGF-independent, the cardiogenic effect of IGFBP-4 was attenuated by IGFs through IGFBP-4 sequestration IGFBP-4 is therefore an inhibitor of the canonical Wnt signalling required for cardiogenesis and provides a molecular link between IGF signalling and Wnt signalling

Insulin and insulin-like growth factor signalling in neoplasia

Abstract: Insulin and insulin-like growth factors (IGFs) are well known as key regulators of energy metabolism and growth. There is now considerable evidence that these hormones and the signal transduction networks they regulate have important roles in neoplasia. Epidermiological, clinical and laboratory research methods are being used to investigate novel cancer prevention and treatment strategies related to insulin and IGF signalling. Pharmacological strategies under study include the use of novel receptor-specific antibodies, receptor kinase inhibitors and AMP-activated protein kinase activators such as metformin. There is evidence that insulin and IGF signalling may also be relevant to dietary and lifestyle factors that influence cancer risk and cancer prognosis. Recent results are encouraging and have justified the expansion of many translational research programmes.

Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles.

Abstract: Most present nanodrug delivery systems have been developed to target cancer cells but rarely nuclei. However, nuclear-targeted drug delivery is expected to kill cancer cells more directly and efficiently. In this work, TAT peptide has been employed to conjugate onto mesoporous silica nanoparticles (MSNs-TAT) with high payload for nuclear-targeted drug delivery for the first time. Monodispersed MSNs-TAT of varied particle sizes have been synthesized to investigate the effects of particle size and TAT conjugation on the nuclear membrane penetrability of MSNs. MSNs-TAT with a diameter of 50 nm or smaller can efficiently target the nucleus and deliver the active anticancer drug doxorubicin (DOX) into the targeted nucleus, killing these cancer cells with much enhanced efficiencies. This study may provide an effective strategy for the design and development of cell-nuclear-targeted drug delivery.