Of Mice and Men . . . and Microbes: Conclusions and Cautions from a Murine Study of the Lung Microbiome and Microbiome-Immune Interactions.
Of Mice and Men . . . and Microbes: Conclusions and Cautions from a Murine Study of the Lung Microbiome and Microbiome-Immune Interactions.
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老鼠和人。
DOI：
10.1164/rccm.201803-0586ed
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发表时间：
2018
影响因子：
24.7
通讯作者：
Collman,RonaldG
中科院分区：
文献类型：
--
作者：
McGinniss,JohnE;Collman,RonaldG
这项研究呼吁注意简化模型系统在纤维化研究中的优势和劣势。值得称赞的是，研究人员使用互补的方法清楚地表明，IPF-ECM通过与使用刚度控制水凝胶报道的机械转导层次不同的机制调节miR-29。然而，这些结果要求我们调和不同模型系统产生的不一致结果。基质因子对成纤维细胞生物学至关重要，将不同的基质条件纳入实验设计可以提供重要的机制见解（1，6）。然而，它也要求对不同层次的复杂性的理解。水凝胶允许控制刚度和ECM配体，但缺乏维度、基质-蛋白质相互作用和交联。脱细胞基质纳入维度，保留天然蛋白质生物化学，并保持区域基质机械性能。然而，它们的生产可能是劳动密集型的，并且难以预测（14）。此外，组织加工对蛋白聚糖和糖胺聚糖、蛋白质构象、基质体蛋白相互作用以及基质中所含的酶/生长因子的影响都知之甚少。这两种方法都不能复制拉伸的体内效应，也不能概括在化学和机械变化基质的背景下在时间和空间上相互作用的多种驻留和募集细胞类型的效应。随着复杂性的增加，对实验变量的控制减少，深入研究特定机械生物学的能力也减少。随着时间的推移，组织工程可能会提高我们研究完整系统的能力（14）。尽管如此，在目前的研究中使用体内异种移植模型提供了信心，miRNA加工机制可以对纤维化具有关键作用。这是否代表IPF的“答案”还有待观察，但它可能代表“一个”答案的证据表明该领域正在取得进展。
This study calls attention to the strengths and weaknesses of reductionist model systems in the study of fibrosis. Laudably, the investigators used complementary approaches to clearly show that the IPF-ECM regulates miR-29 through mechanisms that are distinct from the mechanotransduction hierarchies reported using stiffnesscontrolled hydrogels. However, the results require that we reconcile the discordant findings generated from the different model systems. Matrix factors are critical to fibroblast biology, and incorporation of different matrix conditions into experimental design can provide important mechanistic insights (1, 6). However, it also demands appreciation of different levels of complexity. Hydrogels allow control of stiffness and ECM ligands, but lack dimensionality, matrix–protein interactions, and cross-linking. Decellularized matrices incorporate dimensionality, preserve native protein biochemistry, and maintain regional matrix mechanical properties. Nevertheless, they can be labor-intensive to produce and difficult to predict (14). Moreover, the effects of tissue processing on proteoglycans and glycosaminoglycans, on protein conformation, on matrisome protein interactions, and on the enzymes/growth factors harbored within the matrix are all poorly understood. Neither approach replicates the in vivo effects of stretch or recapitulates the effect of multiple resident and recruited cell types interacting in time and space in the context of a chemically and mechanically changing matrix. With increasing complexity, control of experimental variables diminishes, as does the ability to study specific mechanistic biology in depth. In time, tissue engineering may improve our ability to study intact systems (14). Nevertheless, the use of in vivo xenograft models in the current study provides confidence that the miRNA processing machinery can have a critical effect on fibrogenesis. Whether this represents “the” answer for IPF remains to be seen, but the evidence that it could represent “an” answer is indicative of ongoing progress in the field.■
影响因子：
30.3
作者：
Fujimura KE;Lynch SV
通讯作者：
Lynch SV
DOI：
10.1164/rccm.201403-0541oc
发表时间：
2014-10-15
影响因子：
24.7
作者：
Molyneaux, Phillip L.;Cox, Michael J.;Moffatt, Miriam F.
通讯作者：
Moffatt, Miriam F.