Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage.

HYPERGLYCEMIA IN THE ABSENCE OF CILIA ACCELERATES CYSTOGENESIS AND INDUCES RENAL DAMAGE. Am J Physiol Renal Physiol. 2015 Apr 22;:ajprenal.00652.2014 Authors: Sas KM, Yin H, Fitzgibbon WR, Baicu CF, Zile MR, Steele SL, Amria MY, Saigusa T, Funk JA, Bunni MA, Siegal GP, Siroky BJ, Bissler JJ, Bell PD Abstract In polycystic kidney disease (PKD) the rate of cyst formation and disease progression is highly variable. The lack of predictability in disease progression may be due to additional environmental factors or pathophysiological processes called "third-hits". Diabetes is a growing epidemic and recent studies suggest that PKD patients may be at an increased risk for this disease. We sought to determine if hyperglycemia enhances the initiation and rate of cystogenesis. Adult ift88 conditional floxed allele mice were administered tamoxifen to induce cilia loss in the presence of cre. Subsequent administration of streptozotocin resulted in equivalent hyperglycemia in both cilia (+) and cilia (-) mice. Hyperglycemia with loss of cilia increased the rate of cyst formation and cell proliferation. There were also structural and functional alterations in the kidney, including focal glomerular foot process effacement, interstitial inflammation, formation of primitive renal tubules, polyuria and increased proteinuria in cilia (-) hyperglycemic mice. Gene array analysis indicated enhanced Wnt and epithelial to mesenchymal transition signaling in...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research