MMPs regulate both development and immunity in the tribolium model insect.
MMPs regulate both development and immunity in the tribolium model insect.
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DOI：
10.1371/journal.pone.0004751
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Altincicek B
中科院分区：
文献类型：
--
作者：
Knorr E;Schmidtberg H;Vilcinskas A;Altincicek B
基质金属蛋白酶（MMPs）是一种进化上保守的多功能效应分子。尽管先前在体外和细胞培养中进行了深入的研究，但它们在体内的多效性功能仍然没有得到很好的理解。我们表明，遗传上顺从的甲虫赤拟谷盗是一个可行的模式生物，探索MMP在体内的功能。我们通过dsRNA介导的遗传干扰（RNAi）沉默了三种昆虫型拟谷盗MMP旁系同源物及其生理抑制剂TIMP和RECK的表达。敲低MMP-1的蛹形态发生过程中的发展，给予改变的触角，复眼，翅膀，腿和头的表型。亲本RNAi介导的MMP-1或MMP-2的敲低分别导致幼虫具有非致死性气管缺陷和异常肠，这暗示了MMPs在甲虫胚胎发生过程中的额外作用。这与果蝇（Drosophila melanogaster）的发现不同，果蝇中MMPs在胚胎发生中的作用可以忽略不计。我们的研究结果还表明，MMPs的多效性作用是必要的适当的昆虫先天免疫，因为Tribolium MMP-1的系统性敲低导致显着更高的易感性昆虫病原真菌球孢白僵菌。此外，MMP-1，TIMP和RECK的mRNA水平，以及MMP酶活性在免疫活性血细胞刺激后显着升高。为了证实Tribolium MMP-1的胶原蛋白溶解活性，我们生产并纯化重组酶，并测定了与最相关的人MMP MMP-19相似的胶原蛋白IV降解活性。据我们所知，这是第一项研究，调查几乎所有昆虫MMP旁系同源物沿着其抑制剂TIMP和RECK在昆虫发育和免疫中的体内作用。我们的研究结果表明，从赤拟谷盗模式昆虫，MMPs调节气管和肠道发育过程中的甲虫胚胎发育，蛹形态发生，先天免疫防御反应，从而揭示了MMPs的进化保守的作用。
Matrix metalloproteinases (MMPs) are evolutionarily conserved and multifunctional effector molecules in development and homeostasis. In spite of previous, intensive investigation in vitro and in cell culture, their pleiotrophic functions in vivo are still not well understood. We show that the genetically amenable beetle Tribolium castaneum represents a feasible model organism to explore MMP functions in vivo. We silenced expression of three insect-type Tribolium MMP paralogs and their physiological inhibitors, TIMP and RECK, by dsRNA-mediated genetic interference (RNAi). Knock-down of MMP-1 arrested development during pupal morphogenesis giving phenotypes with altered antennae, compound eyes, wings, legs, and head. Parental RNAi-mediated knock-down of MMP-1 or MMP-2 resulted in larvae with non-lethal tracheal defects and with abnormal intestines, respectively, implicating additional roles of MMPs during beetle embryogenesis. This is different to findings from the fruit fly Drosophila melanogaster, in which MMPs have a negligible role in embryogenesis. Confirming pleiotrophic roles of MMPs our results also revealed that MMPs are required for proper insect innate immunity because systemic knock-down of Tribolium MMP-1 resulted in significantly higher susceptibility to the entomopathogenic fungus Beauveria bassiana. Moreover, mRNA levels of MMP-1, TIMP, and RECK, and also MMP enzymatic activity were significantly elevated in immune-competent hemocytes upon stimulation. To confirm collagenolytic activity of Tribolium MMP-1 we produced and purified recombinant enzyme and determined a similar collagen IV degrading activity as observed for the most related human MMP, MMP-19. This is the first study, to our knowledge, investigating the in vivo role of virtually all insect MMP paralogs along with their inhibitors TIMP and RECK in both insect development and immunity. Our results from the Tribolium model insect indicate that MMPs regulate tracheal and gut development during beetle embryogenesis, pupal morphogenesis, and innate immune defense reactions thereby revealing the evolutionarily conserved roles of MMPs.
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影响因子：
11.2
作者：
Jost, Maud;Folgueras, Alicia R.;Noel, Agnes
通讯作者：
Noel, Agnes
DOI：
10.1073/pnas.48.6.1014
发表时间：
1962-01-01
影响因子：
11.1
作者：
GROSS, J;LAPIERE, CM
通讯作者：
LAPIERE, CM
影响因子：
6.5
作者：
Huelsenbeck, JP;Rannala, B
通讯作者：
Rannala, B
影响因子：
3.1
作者：
Altincicek, Boran;Linder, Monica;Vilcinskas, Andreas
通讯作者：
Vilcinskas, Andreas
DOI：
10.1155/2000/79045
发表时间：
2000-01-01
期刊：
Developmental immunology
影响因子：
--
作者：
Madri, J A;Graesser, D
通讯作者：
Graesser, D