Acute kidney injury induces hallmarks of polycystic kidney disease.

Acute kidney injury induces hallmarks of polycystic kidney disease. Am J Physiol Renal Physiol. 2016 Aug 3;:ajprenal.00167.2016 Authors: Kurbegovic A, Trudel M Abstract Acute kidney injury (AKI) and autosomal dominant polycystic kidney disease (ADPKD) are considered separate entities that both frequently cause renal failure. Since ADPKD appears to depend on Pc1- or Pc2-dosage mechanism, we investigated whether slow progression of cystogenesis in two Pkd1 transgenic mouse models can be accelerated with moderate ischemia-reperfusion injury (IRI). Transient unilateral left ischemic kidney in both non-transgenic and transgenic mice reproducibly develop tubular dilatations, cysts and typical PKD cellular defects within 3 months post-IRI. Similar onset and severity of IRI induced-cystogenesis independently of genotype revealed that IRI is sufficient to promote renal cyst formation, however this response was not further amplified by the transgene in Pkd1 mouse models. The IRI non-transgenic and transgenic kidneys showed from 16 days post-IRI, strikingly increased and sustained Pkd1/Pc1 (>3-fold) and Pc2 (>8-fold) expression that can individually be cystogenic in mice. In parallel, long-term and important stimulation of Hif1α expression was induced as in polycystic kidney disease. While mTOR signaling is activated, stimulation of the Wnt pathway, with markedly increased active β-catenin and c-Myc expression in IRI renal epithelium, u...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research