細(xì)菌大量存在于許多動(dòng)物的腸道中，然而科學(xué)家對(duì)宿主如何在這些細(xì)菌面前保持其組織的完好性卻一直缺乏相關(guān)的了解,。瑞士科學(xué)家在最近一期的《基因與發(fā)育》雜志中指出,，在受外來細(xì)菌激發(fā)后,，黑腹果蠅（Drosophila melanogaster）腸道上皮細(xì)胞的修復(fù)需要一種氧化裂解以及多條信號(hào)通道來完成,。
由NADPH雙氧化酶（Duox）調(diào)控的一種氧化裂解是黑腹果蠅腸道的免疫響應(yīng)的一部分,。這會(huì)使腸道壁受損，從而要求上皮細(xì)胞通過腸內(nèi)干細(xì)胞（ISCs）的增殖來修復(fù),。瑞士洛桑市全球健康研究所的Nicolas Buchon和同事發(fā)現(xiàn),，在響應(yīng)非共生細(xì)菌Ecc15的激發(fā)時(shí)，抗氧化劑能夠減少黑腹果蠅的腸內(nèi)干細(xì)胞增殖,。而抑制Duox同樣能夠在Ecc15存在的前提下減少腸內(nèi)干細(xì)胞的增殖,，這意味著氧化裂解在腸道組織增殖性修復(fù)的開始過程中扮演了一個(gè)重要角色。
在被Ecc15激發(fā)的黑腹果蠅中,，一部分轉(zhuǎn)錄的JAK—STAT通道（這將有助于控制干細(xì)胞在黑腹果蠅中的增殖）,，以及JNK通道（這主要涉及了年老黑腹果蠅腸道的組織完好性的調(diào)控）使得轉(zhuǎn)錄水平被上調(diào)了。研究人員發(fā)現(xiàn),，抑制任意一條通道的信號(hào)都能夠在Ecc15存在的情況下防止腸內(nèi)干細(xì)胞的增殖,。此外，他們發(fā)現(xiàn),，一種被JAK—STAT通道上調(diào)的蛋白質(zhì)——Upd3——在向干細(xì)胞發(fā)出信號(hào)從而引發(fā)增殖的過程中扮演了一個(gè)重要角色,。
盡管Ecc15并沒有殺死野生型果蠅，但那些缺乏增殖性響應(yīng)的果蠅在激發(fā)后的4到8天里相繼死亡,。當(dāng)這些果蠅被一種低劑量的病原體激發(fā)后,，一種與野生型果蠅類似的增殖性響應(yīng)被觀察到，但是高劑量則導(dǎo)致了上皮細(xì)胞的損傷及死亡,，這表明修復(fù)通道在某些情況下是不足的,。當(dāng)研究人員將正常修復(fù)的果蠅與無外來感染的果蠅——即在它們的腸道中沒有細(xì)菌——進(jìn)行比較后，他們發(fā)現(xiàn),，在無外來感染的果蠅中,，通過JNK和JAK—STAT通道的信號(hào)與細(xì)胞增殖都減少了。
因此,，似乎組織形態(tài)學(xué)和腸道對(duì)氧化損傷的響應(yīng)是由對(duì)氧化裂解的識(shí)別來維持的,，并且通過JAK—STAT和JNK通道的信號(hào)導(dǎo)致了腸內(nèi)干細(xì)胞的增殖和修復(fù)。（生物谷Bioon.com）
生物谷推薦原始出處：
Genes & Dev. 2009. 23: 2333-2344 doi:10.1101/gad.1827009
Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila
Nicolas Buchon2, Nichole A. Broderick, Sveta Chakrabarti and Bruno Lemaitre1
Global Health Institute, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut epithelium renewal. Here, we addressed how both infectious and indigenous bacteria modulate stem cell activity in Drosophila. We show that the increased epithelium renewal observed upon some bacterial infections is a consequence of the oxidative burst, a major defense of the Drosophila gut. Additionally, we provide evidence that the JAK–STAT (Janus kinase–signal transducers and activators of transcription) and JNK (c-Jun NH2 terminal kinase) pathways are both required for bacteria-induced stem cell proliferation. Similarly, we demonstrate that indigenous gut microbiota activate the same, albeit reduced, program at basal levels. Altered control of gut microbiota in immune-deficient or aged flies correlates with increased epithelium renewal. Finally, we show that epithelium renewal is an essential component of Drosophila defense against oral bacterial infection. Altogether, these results indicate that gut homeostasis is achieved by a complex interregulation of the immune response, gut microbiota, and stem cell activity.
