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Beta-cell beta 1 integrin deficiency affects in utero development of islet growth and vascularization

机译:β细胞β1整联蛋白缺乏影响胰岛生长和血管化的子宫发展

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摘要

The beta 1 integrin subunit contributes to pancreatic beta cell growth and function through communication with the extracellular matrix (ECM). The effects of in vitro and in vivo beta 1 integrin knockout have been extensively studied in mature islets, yet no study to date has examined how the loss of beta 1 integrin during specific stages of pancreatic development impacts beta cell maturation. Beta-cell-specific tamoxifen-inducible Cre recombinase (MIP-CreERT) mice were crossed with mice containing floxed Itgb1 (beta 1 integrin) to create an inducible mouse model (MIP beta 1KO) at the second transition stage (e13.5) of pancreas development. By e19.5-20.5, the expression of beta-cell beta 1 integrin in fetal MIP beta 1KO mice was significantly reduced and these mice displayed decreased beta cell mass, density and proliferation. Morphologically, fetal MIP beta 1KO pancreata exhibited reduced islet vascularization and nascent endocrine cells in the ductal region. In addition, decreased ERK phosphorylation was observed in fetal MIP beta 1KO pancreata. The expression of transcription factors needed for beta-cell development was unchanged in fetal MIP beta 1KO pancreata. The findings from this study demonstrate that beta 1 integrin signaling is required during a transition-specific window in the developing beta-cell to maintain islet mass and vascularization.
机译:β1整联蛋白亚基有助于胰腺β细胞生长和通过与细胞外基质(ECM)连通的功能。在成熟的胰岛中广泛研究了体外和体内β1的影响,但在成熟的胰岛中已经过度研究了迄今为止没有研究已经检查了胰腺发育特定阶段的β1整合蛋白的损失如何影响β细胞成熟。 β-细胞特异性他莫昔芬 - 诱导的CRE重组酶(MIP-Crefert)小鼠与含有氟氧化ITGB1(β11-11-11-11-11-11-11-14)的小鼠交叉,在第二转变阶段(E13.5)产生诱导型小鼠模型(MIPβ100)胰腺发育。通过E19.5-20.5,胎儿MIPβ1KO小鼠β细胞β1整联蛋白的表达显着降低,这些小鼠显示β细胞质量,密度和增殖降低。形态学上,胎儿MIPβ1KO胰腺β在导管区域中表现出降低的胰岛血管化和新生内分泌细胞。此外,在胎儿MIPβ1KO胰腺癌中观察到降低的ERK磷酸化。胎儿MIPβ1KO胰腺癌中β细胞发育所需的转录因子的表达不变。本研究的发现表明,在显影β细胞中的过渡特异性窗口期间需要β1整合蛋白信号,以保持胰岛质量和血​​管化。

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