Deciphering the Kidney Matrisome: Identification and Quantification of Renal Extracellular Matrix Proteins in Healthy Mice

Precise characterization of a tissue's extracellular matrix (ECM) protein composition (matrisome) is essential for biomedicine. However, ECM protein extraction that requires organ-specific optimization is still a major limiting factor in matrisome studies. In particular, the matrisome of mouse kidneys is still understudied, despite mouse models being crucial for renal research. Here, we comprehensively characterized the matrisome of kidneys in healthy C57BL/6 mice using two ECM extraction methods in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS), protein identification, and label-free quantification (LFQ) using MaxQuant. We identified 113 matrisome proteins, including 22 proteins that have not been previously listed in the Matrisome Database. Depending on the extraction approach, the core matrisome (structural proteins) comprised 45% or 73% of kidney ECM proteins, and was dominated by glycoproteins, followed by collagens and proteoglycans. Among matrisome-associated proteins, ECM regulators had the highest LFQ intensities, followed by ECM-affiliated proteins and secreted factors. The identified kidney ECM proteins were primarily involved in cellular, developmental and metabolic processes, as well as in molecular binding and regulation of catalytic and structural molecules' activity. We also performed in silico comparative analysis of the kidney matrisome composition in humans and mice based on publicly available data. These results contribute to the first reference database for the mouse renal matrisome.

Automated summary

Precise characterization of a tissue's extracellular matrix protein composition is crucial for biomedicine. However, extracting the extracellular matrix proteins from specific organs remains a challenge for matrisome studies. In this study, we comprehensively characterized the matrisome of kidneys in healthy mice and identified a total of 113 matrisome proteins, including 22 novel proteins. We also compared the kidney matrisome composition between humans and mice. These findings provide a valuable reference database for studying the renal matrisome in mice.