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首页> 外文期刊>Experimental Biology and Medicine: Journal of the Society for Experimental Biology and Medicine >Expressional difference, distributions of TGF-β1 in TGF-β1 knock down transgenic mouse, and its possible roles in injured spinal cord
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Expressional difference, distributions of TGF-β1 in TGF-β1 knock down transgenic mouse, and its possible roles in injured spinal cord

机译:TGF-β1击倒转基因小鼠的表达差异,TGF-β1的分布及其在脊髓损伤中的可能作用

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Transforming growth factor β1 (TGF-β1) is a multi-functional cytokine implicated in many aspects of mammalian wound healing and scar tissue formation. However, few experiments have so far addressed the potential biological effects of TGF-β1 in the nervous system after injury, in addition to the immune system. In the present study, expressional silencing TGF-β1 was achieved by selecting predesigning hairpins targeting mouse TGF-β1 genes. Four homozygous transgenic offspring were generated and designed as Founder 90, Founder 12, Founder 41 and Founder 46. The down-regulated rates of TGF-β1 in different transgenic mice were also determined. To investigate the potential roles of TGF-β1, we observed changes in the neurological behavior of TGF-β1-knockdown (TGF-β1-kd) mice after spinal cord transection (SCT). Moreover, mRNA levels of inflammatory cytokines, including IL-1, IL-6, IL-10, NF-κB and TNF, were also detected in nucleate cells from blood by real-time PCR. Consequently, different TGF-β1 expressions were detected in multiple tissues, and protein levels of TGF-β1 decreased at different rates relative to that of wild type (WT) ones. The levels of TGF-β1 proteins in TGF-β1-kd mice decreased at most by 57% in Founder 90, which showed a significant recovery in Basso, Beattie, Bresnahan (BBB) scores after SCT compared with that of WT. However, expressions of immune relative genes showed no dramatic difference compared with WT ones. This study is the first to generate TGF-β1 down regulated mice and determine the possible roles of TGF-β1 in vivo in different conditions.
机译:转化生长因子β1(TGF-β1)是一种多功能细胞因子,与哺乳动物伤口愈合和瘢痕组织形成的许多方面有关。然而,到目前为止,除了免疫系统外,几乎没有任何实验解决TGF-β1在损伤后神经系统中的潜在生物学作用。在本研究中,通过选择针对小鼠TGF-β1基因的预先设计的发夹来实现表达沉默TGF-β1。生成了四个纯合的转基因后代,并将其设计为Founder 90,Founder 12,Founder 41和Founder46。还确定了不同转基因小鼠中TGF-β1的下调率。为了研究TGF-β1的潜在作用,我们观察了脊髓横断(SCT)后TGF-β1-敲低(TGF-β1-kd)小鼠神经行为的变化。此外,还通过实时PCR在血液中的有核细胞中检测到了炎性细胞因子的mRNA水平,包括IL-1,IL-6,IL-10,NF-κB和TNF。因此,在多个组织中检测到不同的TGF-β1表达,并且相对于野生型(WT),TGF-β1的蛋白质水平以不同的速率下降。在Founder 90中,TGF-β1-kd小鼠中TGF-β1蛋白的水平最多降低了57%,与WT相比,SCT后Basso,Beattie,Bresnahan(BBB)评分显着恢复。但是,免疫相关基因的表达与野生型相比没有显着差异。这项研究是首次产生TGF-β1下调的小鼠并确定TGF-β1在不同条件下体内的可能作用。

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