Comprehensive profiling of cell type-specific expression and distribution of complement genes in mouse and human kidneys: insights into normal physiology and response to kidney transplantations.

Abstract

Background: Recent studies innovatively revealed the localized expression of complement genes in kidneys and shed light on the vital roles of the intracellular complement system in the physiologic function and pathological conditions. However, a comprehensive analysis of the expression of complement genes in the context of the evolving cellular landscape of the kidney is not available.

Methods: We analyzed single-cell RNA sequencing data from healthy human subjects, C57BL/6 mice, and kidney transplant-rejected mice. The data were sourced from the NCBI Gene Expression Omnibus and processed using quality control measures and unsupervised clustering. Differential gene analyses were based on expression levels.

Results: In total, 50 complement genes were categorized into pattern recognition molecules, proteases, complement components, receptors, and regulators. In normal mice kidneys, complement genes were expressed at relatively low levels. Among different complement gene categories, receptor genes were most widely expressed in kidney cells. Comparatively, macrophages and mesangial cells are the most abundant immune and nonimmune cell types for complement gene expression. A comparison of human and mouse data showed similar expression patterns, but human kidney complement gene expression was more abundant. Comparative analysis between mouse transplant-rejected and normal kidneys demonstrated stronger complement gene expression in transplant-rejected kidneys.

Conclusions: This study illustrated significant similarities in complement gene expression between murine and human kidneys and highlighted the responsive nature of complement genes to kidney injury, underscoring the dynamic nature of local complement regulation. These findings enhance our understanding of the complex regulation of the complement system within the kidney, offering insights into its role in renal disease pathogenesis.