Updated: Jul 7, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
E A Gantsova1,2, O V Serova1, D Eladari3
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the RAS, Moscow 117997, Russia.
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This study explored how a receptor called IRR affects kidney function in mice. Researchers compared gene activity in mice with and without the IRR gene, under normal and high bicarbonate conditions. They found that IRR knockout mice had changes in several genes, including those involved in ATP metabolism and electron transport. One gene, kcnk5, was more active in normal mice after bicarbonate loading but not in IRR knockout mice. These findings suggest that IRR plays a role in regulating kidney genes during acid-base changes. The study helps clarify IRR's function in maintaining pH balance through gene regulation.
Area of Science:
Background:
Regulation of plasma pH is essential for physiological stability. Kidneys maintain acid-base balance by modulating bicarbonate levels. The IRR receptor tyrosine kinase is active in β-intercalated cells and responds to extracellular alkalization. Mice lacking the insrr gene show impaired bicarbonate excretion. The exact role of IRR in kidney gene regulation remains unclear. This gap motivated transcriptomic studies to uncover IRR-dependent pathways. Prior research has shown IRR's involvement in alkali sensing. No prior work had resolved IRR's downstream targets. This paper's contribution is to identify IRR-regulated genes in kidney function.
Purpose Of The Study:
This study aimed to explore how IRR regulates kidney gene expression during bicarbonate loading. The specific problem is to identify genes affected by IRR absence in acid-base regulation. The motivation is to understand IRR's role in renal physiology. The researchers compared transcriptomes of wild-type and IRR knockout mice. They tested gene expression under normal and bicarbonate-loaded conditions. The goal was to find IRR-dependent regulatory patterns. This approach allows for a systems-level view of IRR function. The study focused on β-intercalated cells and their response to pH changes.
IRR knockout mice show altered gene expression in kidney tissues, including ATP metabolic processes.
The kcnk5 gene's expression increases in wild-type mice after bicarbonate loading but not in IRR knockout mice.
IRR is expressed in β-intercalated cells, which are involved in acid-base regulation and bicarbonate secretion.
It identifies enriched biological processes, such as ATP metabolism and electron transport, affected by IRR knockout.
Main Methods:
The researchers used transcriptomic profiling to compare gene expression in mouse kidneys. They examined wild-type and IRR knockout mice under control and bicarbonate-loaded states. RNA sequencing was performed to identify differentially expressed genes. TaqMan real-time PCR validated the expression of selected genes. The study focused on β-intercalated cell-specific genes. Gene set enrichment analysis was used to find enriched pathways. The team compared gene expression changes between genotypes. This approach allowed for identification of IRR-regulated processes.
Main Results:
Transcriptomic analysis showed altered gene expression in IRR knockout mice. The slc26a4, rps7, slc5a2, aqp6, and plcd1 genes were differentially expressed. Gapdh, rny3, kcnk5, slc6a6, and atp6v1g3 also showed expression changes. Bicarbonate loading increased kcnk5 expression in wild-type mice. This increase was absent in IRR knockout mice. Gene set enrichment analysis revealed ATP metabolism and electron transport changes. These findings suggest IRR influences energy-related pathways. The results highlight IRR's role in regulating kidney gene networks.
Conclusions:
IRR knockout mice show altered gene expression in kidney tissues. The findings suggest IRR regulates genes involved in acid-base balance. Bicarbonate loading affects kcnk5 expression in wild-type mice. This effect is not observed in IRR knockout mice. The study supports IRR's role in alkali sensing and gene regulation. ATP metabolic processes are affected in IRR knockout mice. These results may help understand IRR-dependent pathways. The authors propose IRR influences renal gene networks during pH changes.
TaqMan real-time PCR confirmed differential expression of genes like slc26a4, rps7, and kcnk5.
The authors propose IRR influences renal gene networks during pH changes and acid-base regulation.