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胶凝酶 MMP-9 样物质参与调控海鞘的 LPS 炎症反应。

The gelatinase MMP-9like is involved in regulation of LPS inflammatory response in Ciona robusta.

机构信息

Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy; Advanced Technologies Network Center (ATeN), University of Palermo, Palermo, Italy.

Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy.

出版信息

Fish Shellfish Immunol. 2019 Mar;86:213-222. doi: 10.1016/j.fsi.2018.11.028. Epub 2018 Nov 16.

Abstract

Matrix metalloproteinases (MMPs) are a family of endopeptidases collectively able to degrade the components of the extracellular matrix (ECM), with important roles in many biological processes, such as embryogenesis, normal tissue remodelling, angiogenesis and wound healing. New views on the function of MMPs reveal that they regulate inflammatory response and therefore might represent an early step in the evolution of the immune system. MMPs can affect the activity of cytokines involved in inflammation including TGF-β and TNF-α. MMPs are widely distributed in all kingdoms of life and have likely evolved from a single-domain protein which underwent successive rounds of duplications. In this study, we focused on the Ciona robusta (formerly known as Ciona intestinalis) MMP gelatinase homologue. Gene organization, phylogenetic analysis and 3D modeling supported the closest correlation of C. robusta gelatinase with the human MMP-9. Real-time PCR analysis and zymographic assay showed a prompt expression induced by LPS inoculation and an upregulation of enzymatic activity. Furthermore, we showed that before of the well-known increase of TGF-β and TNF-α levels, a MMP-9like boost occurred, suggesting a possible involvement of MMP-9like in regulating inflammatory response in C. robusta.

摘要

基质金属蛋白酶(MMPs)是一类内肽酶,能够共同降解细胞外基质(ECM)的成分,在许多生物学过程中具有重要作用,如胚胎发生、正常组织重塑、血管生成和伤口愈合。对 MMPs 功能的新观点表明,它们调节炎症反应,因此可能代表免疫系统进化的早期步骤。MMPs 可以影响参与炎症的细胞因子的活性,包括 TGF-β 和 TNF-α。MMPs 广泛分布于所有生命领域,可能是由一个经历了连续复制的单结构域蛋白进化而来的。在这项研究中,我们专注于强壮海鞘(以前称为海鞘肠)的 MMP 明胶酶同源物。基因组织、系统发育分析和 3D 建模支持 C. robusta 明胶酶与人类 MMP-9 最密切的相关性。实时 PCR 分析和酶谱分析显示 LPS 接种诱导的快速表达和酶活性的上调。此外,我们还表明,在 TGF-β和 TNF-α水平的显著增加之前,出现了 MMP-9 样的增加,这表明 MMP-9 样可能参与调节强壮海鞘的炎症反应。

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