174 research outputs found

    E2F-1 Directly Regulates Thrombospondin 1 Expression

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    Thrombospondin 1 (TSP1) has been shown to play a critical role in inhibiting angiogenesis, resulting in inhibition of tumor growth and metastases. To figure out TSP1's regulators will lead to reveal its biological function mechanistically. In this study, we show that E2F-1 could activate the transcription of TSP1 by both promoter assays and Northern blot. Analysis of various TSP1 promoter mutant constructs showed that a sequence located −144/−137 up-stream of the transcriptional initiation site, related to the consensus E2F-responsive sequence, is necessary for the activation. In consistence with up-regulation of TSP-1 activity by over-expression of E2F-1, the knockdown of endogenous E2F-1 inhibited TSP-1 promoter activity significantly, implying that E2F-1 mediated regulation of TSP-1 is relevant in vivo. In addition, E2F-1 could also directly bind to the TSP1 promoter region covering −144/−137 region as revealed by ChIP assays. Furthermore, the E2F-1-induced activation of TSP1 gene transcription is suppressed by pRB1 in a dose-dependent manner. Taken together, the results demonstrate that TSP1 is a novel target for E2F1, which might imply that E2F-1 can affect angiogenesis by modulating TSP1 expression

    Thrombospondins in the heart: potential functions in cardiac remodeling

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    Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease

    Evidence for the ‘Good Genes’ Model: Association of MHC Class II DRB Alleles with Ectoparasitism and Reproductive State in the Neotropical Lesser Bulldog Bat, Noctilio albiventris

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    The adaptive immune system has a major impact on parasite resistance and life history strategies. Immunological defence is costly both in terms of immediate activation and long-term maintenance. The ‘good genes’ model predicts that males with genotypes that promote a good disease resistance have the ability to allocate more resources to reproductive effort which favours the transmission of good alleles into future generations. Our study shows a correlation between immune gene constitution (Major Histocompatibility Complex, MHC class II DRB), ectoparasite loads (ticks and bat flies) and the reproductive state in a neotropical bat, Noctilio albiventris. Infestation rates with ectoparasites were linked to specific Noal-DRB alleles, differed among roosts, increased with body size and co-varied with reproductive state particularly in males. Non-reproductive adult males were more infested with ectoparasites than reproductively active males, and they had more often an allele (Noal-DRB*02) associated with a higher tick infestation than reproductively active males or subadults. We conclude that the individual immune gene constitution affects ectoparasite susceptibility, and contributes to fitness relevant trade-offs in male N. albiventris as suggested by the ‘good genes’ model

    Review of the North American jumping mice (genus Zapus)

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    Dissertation (Ph.D.)--University of Kansas, Zoology, 1953

    Pump Handbook

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    xxii, 1341 hal .; ill.;20c
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