The circadian clock network in mammals is responsible for the temporal coordination of numerous physiological processes that are necessary for homeostasis. Peripheral tissues demonstrate circadian rhythmicity and dysfunction of core clock components has been implicated in the pathogenesis of diseases that are characterized by abnormal extracellular matrix, such as fibrosis (too much disorganized matrix) and tissue breakdown (too little matrix). Kidney disease is characterized by proteinuria, which along with the rate of filtration, displays robust circadian oscillation. Clinical observation and mouse studies suggest the presence of 24-hourly kidney clocks responsible for circadian oscillation in kidney function. Recent experimental evidence has also revealed that cell-matrix interactions and the biomechanical properties of extracellular matrix have key roles in regulating peripheral circadian clocks and this mechanism appears to be cell- and tissue-type specific. Thus, establishing a temporally resolved kidney matrisome may provide a useful tool for studying the two-way interactions between the extracellular matrix and the intracellular time-keeping mechanisms in this critical niche tissue. This review summarizes the latest genetic and biochemical evidence linking kidney physiology and disease to the circadian system with a particular focus on the extracellular matrix. We also review the experimental approaches and methodologies required to dissect the roles of circadian pathways in specific tissues and outline the translational aspects of circadian biology, including how circadian medicine could be used for the treatment of kidney disease.

哺乳动物的生物钟网络负责体内平衡所必需的众多生理过程的时间协调。外周组织表现出昼夜节律性和核心时钟成分的功能障碍与以异常细胞外基质为特征的疾病的发病机制有关，例如纤维化（过多的无组织基质）和组织分解（太少的基质）。肾脏疾病的特征是蛋白尿，它与滤过率一起显示出强烈的昼夜节律振荡。临床观察和小鼠研究表明，存在负责肾功能昼夜节律振荡的 24 小时肾脏时钟。最近的实验证据还表明，细胞-基质相互作用和细胞外基质的生物力学特性在调节外周生物钟方面起着关键作用，并且这种机制似乎是细胞和组织类型特异性的。因此，建立一个暂时解决的肾脏基质体可能为研究细胞外基质和细胞内时间保持机制在这个关键的利基组织中的双向相互作用提供了一个有用的工具。这篇综述总结了将肾脏生理学和疾病与昼夜节律系统联系起来的最新遗传和生化证据，特别关注细胞外基质。