The kidney‐specific expression of genes can be modulated by the extracellular osmolality

Abstract

With this study, we wanted to prove the hypothesis that the unique extracellular osmolality within the renal medulla modulates a specific gene expression pattern. The physiologic functions of the kidneys are mediated by the segment-specific expression of key proteins. So far, we have limited knowledge about the mechanisms that control this gene expression pattern. The hyperosmolality in the renal medullary interstitium is of major importance as a driving force for urine concentration. We made use of primarily cultured rat renal inner medullary collecting-duct cells and microarray analysis to identify genes affected by the environmental osmolality of the culture medium. We identified hundreds of genes that were either induced or repressed in expression by hyperosmolality in a time- and osmolality-dependent fashion. Further analysis demonstrated that many of them, physiologically, showed a kidney- and even collecting-duct-specific expression, including secreted proteins, kinases, and transcription factors. On the other hand, we identified factors, down-regulated in expression, that have a diuretic effect. In conclusion, the kidney is the only organ that has such a hyperosmotic environment, and study provides an excellent method for controlling tissue-specific gene expression.-Schulze Blasum, B., Schröter, R., Neugebauer, U., Hofschröer, V., Pavenstädt, H., Ciarimboli, G., Schlatter E., Edemir, B. The kidney-specific expression of genes can be modulated by the extracellular osmolality.

Genome-Wide Gene–Potassium Interaction Analyses on Blood Pressure

“…Our finding is further supported by a recent functional study, in which extracellular osmolality within the renal medulla up-regulated the expression of RanBP3L. 37 The RANBP3L signal may have also reflect other genes in this locus. For example, a nearby gene, SKP2 encoding S-phase kinase associated protein 2, interacts with p27 and promotes p27 degradation 38 .…”

Lithium Chloride and GSK3 Inhibition Reduce Aquaporin-2 Expression in Primary Cultured Inner Medullary Collecting Duct Cells Due to Independent Mechanisms

“…Primary cultured IMCD cells were prepared as previously described [16]. Female Wistar rats at the age of 23 months were sacrificed by decapitation and the kidneys were removed.…”

“…Total RNA and cDNA synthesis were performed as described before [16]. Real-time PCR was performed using the SYBR Green PCR Master Mix with the ABI PRISM 7900 Sequence Detection System.…”

Hypertonicity-Affected Genes Are Differentially Expressed in Clear Cell Renal Cell Carcinoma and Correlate with Cancer-Specific Survival

“…The effect of hyper-osmolality on gene expression can be reverted by hypo osmotic switch [4]. For example one of the hypertonicity-induced transcripts (0 fragments per kilobase of transcript per million mapped reads (FPKM) at 300 vs. 75 FPKM at 900 mosmol/kg, see Table S1) was the E74-like ETS transcription factor 5 (ELF5).…”

“…However, as mentioned by Lindgren et al [1], the transcriptional cues that determine segment-specific gene expression patterns are only partly understood. We have recently shown that the unique hypertonicity in the renal inner medulla regulates kidney and nephron-specific gene expression [4]. The group of Prof. Ian Frew showed that deletion of renal expression of the tumor suppressor von Hippel-Lindau (VHL) protein altered the urine concentration capability in mice [5].…”