Dysregulated extracellular matrix is the hallmark of fibrosis, and it has a profound impact on kidney function in disease. Furthermore, perturbation of matrix homeostasis is a feature of aging and is associated with declining kidney function. Understanding these dynamic processes, in the hope of developing therapies to combat matrix dysregulation, requires the integration of data acquired by both well-established and novel technologies. Owing to its complexity, the extracellular proteome, or matrisome, still holds many secrets and has great potential for the identification of clinical biomarkers and drug targets. The molecular resolution of matrix composition during aging and disease has been illuminated by cutting-edge mass spectrometry–based proteomics in recent years, but there remain key questions about the mechanisms that drive altered matrix composition. Basement membrane components are particularly important in the context of kidney function; and data from proteomic studies suggest that switches between basement membrane and interstitial matrix proteins are likely to contribute to organ dysfunction during aging and disease. Understanding the impact of such changes on physical properties of the matrix, and the subsequent cellular response to altered stiffness and viscoelasticity, is of critical importance. Likewise, the comparison of proteomic data sets from multiple organs is required to identify common matrix biomarkers and shared pathways for therapeutic intervention. Coupled with single-cell transcriptomics, there is the potential to identify the cellular origin of matrix changes, which could enable cell-targeted therapy. This review provides a contemporary perspective of the complex kidney matrisome and draws comparison to altered matrix in heart and liver disease.

细胞外基质失调是纤维化的标志，对疾病中的肾功能具有深远影响。此外，基质稳态的扰动是衰老的一个特征，并且与肾功能下降有关。了解这些动态过程，希望开发出对抗基质失调的疗法，需要整合通过成熟技术和新技术获得的数据。由于其复杂性，细胞外蛋白质组或基质体仍然隐藏着许多秘密，并且在鉴定临床生物标志物和药物靶标方面具有巨大潜力。近年来，基于质谱的尖端蛋白质组学阐明了衰老和疾病过程中基质成分的分子分辨率，但关于驱动基质成分改变的机制仍然存在关键问题。基底膜成分在肾功能方面尤为重要；来自蛋白质组学研究的数据表明，基底膜和间质基质蛋白之间的转换可能会导致衰老和疾病期间的器官功能障碍。了解这种变化对基质物理特性的影响，以及随后细胞对刚度和粘弹性改变的反应，至关重要。同样，需要比较来自多个器官的蛋白质组数据集，以确定共同的基质生物标志物和治疗干预的共享途径。结合单细胞转录组学，有可能识别基质变化的细胞起源，这可以实现细胞靶向治疗。这篇综述提供了复杂肾脏基质体的当代视角，并与心脏和肝脏疾病中改变的基质进行了比较。