A comprehensive analysis of gene expression profiles in distal parts of the mouse renal tubule

Abstract

The distal parts of the renal tubule play a critical role in maintaining homeostasis of extracellular fluids. In this review, we present an in-depth analysis of microarray-based gene expression profiles available for microdissected mouse distal nephron segments, i.e., the distal convoluted tubule (DCT) and the connecting tubule (CNT), and for the cortical portion of the collecting duct (CCD; Zuber et al., Proc Natl Acad Sci USA 106: [16523][16524][16525][16526][16527][16528] 2009). Classification of expressed transcripts in 14 major functional gene categories demonstrated that all principal proteins involved in maintaining the salt and water balance are represented by highly abundant transcripts. However, a significant number of transcripts belonging, for instance, to categories of Gprotein-coupled receptors or serine/threonine kinases exhibit high expression levels but remain unassigned to a specific renal function. We also established a list of genes differentially expressed between the DCT/CNT and the CCD. This list is enriched by genes related to segment-specific transport functions and by transcription factors directing the development of the distal nephron or collecting ducts. Collectively, this in silico analysis provides comprehensive information about relative abundance and tissue specificity of the DCT/ CNT and the CCD expressed transcripts and identifies new candidate genes for renal homeostasis.

Protein Phosphatase 1 Inhibitor-1 Deficiency Reduces Phosphorylation of Renal NaCl Cotransporter and Causes Arterial Hypotension

“…Using freehand microdissection, previous studies established transcriptome data for the renal distal convolution, 21,22 but the gradual transition from the DCT to the connecting tubule makes it almost impossible to precisely define the border between these functionally different segments. Moreover, the low yield of microdissection requires amplification of obtained cDNAs, which bears the risk of increased false-positive and false-negative results.…”

“…To test for functional effects, we injected Xenopus oocytes with cRNAs encoding NCC together with PP1a, the catalytic subunit of PP1, or a constitutively active variant of I-1 (T35D). 31 I-1 (T35D) substantially increased 22 Na uptake ( Figure 3B). PP1a slightly reduced 22 Na uptake, but the differences did not reach statistical significance.…”

“…31 I-1 (T35D) substantially increased 22 Na uptake ( Figure 3B). PP1a slightly reduced 22 Na uptake, but the differences did not reach statistical significance. The heterologous overexpression of PP1a may not have been sufficient to overcome the known high activity of endogenous PP1 in the oocyte.…”

“…Therefore, we hypothesized that the DCT may express a particular set of DCT-enriched gene products, of which at least some participate in the regulation of NCC-mediated sodium absorption. Encouraged by previous gene expression analysis on freehand-isolated renal tubules in the works by Chabardès-Garonne et al, 20 Cheval et al, 21 and Pradervand et al, 22 we aimed at identifying DCT-enriched gene products using a transcriptomic approach. We used complex object parametric analysis and sorting (COPAS) of renal tubules, which was developed by Miller et al, 23 to isolate DCTs on a large scale.…”

New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors

“…However, the GPCRs discussed here may only be the tip of the iceberg. Indeed, by analyzing transcriptomic data, Pradervand et al [214] have identified In our opinion, the next important challenge is not only to discover new regulatory processes but also to understand how they are linked. As shown in this review, the activation of some GPCRs induces the stimulation of Na + reabsorption whereas others trigger the inhibition of Na + transport.…”