Altered renal morphology in transgenic mice with cholecystokinin overexpression

Abstract

Although cholecystokinin is a regulatory peptide with a predominant role in the brain and the gastrointestinal tract, there is an increasing evidence for its role in the kidney. The aim of this study was to reveal morphological changes in the structure of kidney of mice with cholecystokinin overexpression by means of light, transmission and scanning electron microscope, and atomic force microscopy. Using immunohistochemistry the expression of important basement membrane proteins collagen IV, laminin and fibronectin, as well the distribution of cholecystokinin-8 in the renal structures was evaluated. The altered morphology of kidneys of mice with cholecystokinin overexpression was seen by all microscopic techniques used. The renal corpuscles were relatively small with narrow capsular lumen. The basement membranes of renal tubules were thickened and the epithelial cells were damaged, which was more pronounced for distal tubules. Characteristic feature was the increased number of vesicles seen throughout the epithelial cells of proximal and especially in distal tubules reflecting to the enhanced cellular degeneration. The relative expression of laminin but not collagen IV in the glomerular basement membrane was higher than in the tubular basement membranes. The content of fibronectin, in opposite, was higher in tubular membranes. Cholecystokinin-8 was clearly expressed in the glomeruli, in Bowman's capsule, in proximal and distal tubules, and in collecting ducts. Ultrastructural studies showed irregularly thickened glomerular basement membranes to which elongated cytopodia of differently shaped podocytes were attached. As foot processes were often fused the number of filtration pores was decreased. In conclusion, cholecystokinin plays important role in renal structural formation and in functioning as different aspects of urine production in mice with cholecystokinin overexpression are affected-the uneven glomerular basement membrane thickening, structural changes in podocytes and in filtration slits affect glomerular filtration, while damaged tubular epithelial cells and changed composition of thickened tubular basement membranes affect reabsorption.

Cholecystokinin Plays a Novel Protective Role in Diabetic Kidney Through Anti-inflammatory Actions on Macrophage

“…Aunapuu et al (42) recently reported that CCK overexpression was associated with renal morphological damage in transgenic mice without a significant difference in kidney weight or proteinuria, but with a thickened glomerular basement membrane. CCK is expressed from embryonic day (E) 8.5, whereas both CCK-1R and CCK-2R have been identified from E10.5; in addition, CCK is thought to affect tissue growth and differentiation (43).…”

Gastrin, Cholecystokinin, Signaling, and Biological Activities in Cellular Processes

“…As classical gut hormones and potent neurotransmitters, gastrin and CCK are widely distributed in gastrointestinal tract, CNS, and peripheral neurons (4,18). However, CCK has also been suggested to stimulate spermatozoan fertilization, exert anti-inflammatory effects, promote sodium excretion into the urine, and predict the risk of mortality in heart failure, consistent with its expression in male germ cells (19), cells of immune system (20)(21)(22)(23), renal cortex and medulla (24), and cardiomyocytes (25), respectively.…”

Low Protein Diet Inhibits Uric Acid Synthesis and Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats

“…The extent of mesangial expansion of each group was calculated as sums of the score of each proliferation degree [11]. Tubular damage was evaluated according to the degrees of hyaline degeneration of tubular epithelial cells and quantitatively scored in each group as previously described [12]. …”