A new secreted protein that binds to Wnt proteins and inhibits their activities

The Wnt proteins constitute a large family of extracellular signalling molecules that are found throughout the animal kingdom and are important for a wide variety of normal and pathological developmental processes. Here we describe Wnt-inhibitory factor-1 (WIF-1), a secreted protein that binds to Wnt proteins and inhibits their activities. WIF-1 is present in fish, amphibia and mammals, and is expressed during Xenopus and zebrafish development in a complex pattern that includes paraxial presomitic mesoderm, notochord, branchial arches and neural crest derivatives. We use Xenopus embryos to show that WIF-1 overexpression affects somitogenesis (the generation of trunk mesoderm segments), in agreement with its normal expression in paraxial mesoderm. In vitro, WIF-1 binds to Drosophila Wingless and Xenopus Wnt8 produced by Drosophila S2 cells. Together with earlier results obtained with the secreted Frizzled-related proteins, our results indicate that Wnt proteins interact with structurally diverse extracellular inhibitors, presumably to fine-tune the spatial and temporal patterns of Wnt activity.     

Insulin binds to brain blood vessels in vivo.

The brain has generally been considered an insulin-independent organ, because insulin does not apparently exert a direct effect on brain glucose consumption. Recently, however, insulin receptors have been detected throughout the central nervous system (CNS) of several species. Since important insights into the functional significance of brain insulin receptors might be provided by identification of the cell type(s) possessing these receptors, we have attempted to localise them morphologically using light and electron microscope autoradiography. We report here results indicating that blood vessels throughout the CNS of the rat bind plasma insulin rapidly and with considerable specificity.     

Adrenomedullin inhibits the endothelin production in-duced by urotensin Ⅱ in rat vascular smooth muscle cells

The aim of this study was to observe the effects of adrenomedullin (ADM) on endothelin (ET) production induced by urotensin Ⅱ (UⅡ) in rat vascular smooth muscle cells (VSMCs). Cultured VSMCs which were incubated with UⅡ (10-8 mol/L) and with various concentrations of ADM were used to measure the VSMCs 3H-TdR incorpora-tion, the activity of extracellular signal-regulated kinase(ERK), the amount of ET mRNA and ET production inVSMCs. In this work we found that incubation with UⅡ(10-8 mol/L) increased obviously the amount of ET mRNA inVSMCs and ET production in medium, however,co-incubation with ADM (10-10-10-8 mol/L) and UⅡ(10-8mol/L) reduced the amount of ET mRNA by 15%, 24% and45% (P< 0.01) respectively, compared with UⅡ alone. Thecontent of ET in medium was 14.13, 11.38 and 11.00 pg/mL. ADM alone (10-8 mol/L) had no effect on ET production inVSMCs. UⅡ (10-8 mol/L) promoted the 3H-TdR incorpo-ration and activity of ERK in VSMCs. ADM inhibited VSMCs 3H-TdR incorporation and activation of ERK in aconcentration-dependent manner. Compared with UⅡgroup, after co-incubation with ADM (10-10-10-8 mol/L)and UⅡ (10-8 mol/L) the VSMCs 3H-TdR incorporation wasdecreased by 7% (P > 0.05), 32% (P < 0.05) and 41% (P <0.01), respectively, and the activity of ERK was decreasedby 24% (P > 0.05), 32% (P < 0.05) and 36% (P < 0.05), re-spectively, in a concentration-dependent manner. The resultsshow that in cultured VSMCs ADM inhibits ET mRNA ex-pression, ET production and proliferation stimulated by UⅡ, and that inhibitory effect of ADM on UⅡ bioaction could be mediated through inhibiting MAPK pathway.     

Adrenomedullin inhibits the endothelin production induced by urotensin II in rat vascular smooth muscle cells

The aim of this study was to observe the effects of adrenomedullin (ADM) on endothelin (ET) production induced by urotensin Ⅱ (UⅡ) in rat vascular smooth muscle cells (VSMCs). Cultured VSMCs which were incubated with UⅡ (10^-8 mol/L) and with various concentrations of ADM were used to measure the VSMCs ³H-TdR incorpora- tion, the activity of extracellular signal-regulated kinase (ERK), the amount of ET mRNA and ET production in VSMCs. In this work we found that incubation with UⅡ(10^-8 mol/L) increased obviously the amount of ET mRNA in VSMCs and ET production in medium, however, coincubation with ADM (10^-10—10^-8 mol/L) and UⅡ(10^-8 mol/L) reduced the amount of ET mRNA by 15%, 24% and 45% (P< 0.01) respectively, compared with UⅡ alone. The content of ET in medium was 14.13, 11.38 and 11.00 pg/mL. ADM alone (10^-8 mol/L) had no effect on ET production in VSMCs. UⅡ (10^-8 mol/L) promoted the 3H-TdR incorpo- ration and activity of ERK in VSMCs. ADM inhibited VSMCs 3H-TdR incorporation and activation of ERK in a concentration-dependent manner. Compared with UⅡ group, after coincubation with ADM (10^-10—10^-8 mol/L) and UⅡ (10^-8 mol/L) the VSMCs 3H-TdR incorporation was decreased by 7% (P > 0.05), 32% (P < 0.05) and 41% (P < 0.01), respectively, and the activity of ERK was decreased by 24% (P > 0.05), 32% (P < 0.05) and 36% (P < 0.05), re- spectively, in a concentration-dependent manner. The results show that in cultured VSMCs ADM inhibits ET mRNA expression, ET production and proliferation stimulated by UⅡ, and that inhibitory effect of ADM on UⅡ bioaction could be mediated through inhibiting MAPK pathway.