Abstract 16847: C-kit+ Cells Restore Podocyte Function in a Model of Acute Glomerulonephritis in Rats
Introduction: Kidney-derived c-kit cells exhibit the properties of stem cells and regenerate epithelial tubular cells following ischemia-reperfusion injury. We hypothesize that c-kit+ cells have the capacity to improve podocyte function in a model of acute glomerulonephritis induced by puromycin aminonucleoside (PAN).
Methods: A single dose of PAN (15 mg/100g) was administered intraperitoneally into 2-month-old female Sprague-Dawley rats. After 5 days, animals were injected with saline or c-kit cells. Metabolic parameters (serum creatinine, blood urea nitrogen [BUN] and urinary ratio of albumin/creatinine), and histologic and gene expression analyses were performed at 10 and 21 days.
Results: C-kit treated animals exhibited lower values of BUN after 10 days compared to the saline group (92 mg/dL vs 58.2 mg/dL, P<0.001). At 21 days, kidney weight was lower in c-kit-treated animals (0.5 g/100 g body weight [BW]) compared to saline treated animals (0.54 g/100 g BW, P=0.024). Urinary ratio of albumin/creatinine was lower in c-kit treated animals (0.77±0.46 g/mg) compared to the saline group (1.15±0.77 g/mg). A few c-kit+ cells were engrafted into the tubule-interstitial compartment. Expression of CD2AP and α-actin 4 (involved in podocyte cytoskeleton) and mTOR (mammalian target of rapamycin) were up-regulated after 21 days in the c-kit treated group. Of importance, Raptor/Rictor ratio was lower in c-kit treated animals compared to the saline group (1.17 vs 1.78, P = 0.029). Rictor expression was comparable between c-kit treated animals and normal kidneys, but was higher than the expression observed in the saline treated group (P<0.05). Autophagy was less efficient in the saline group compared to the c-kit treated group when the number of autophagosomes/autophagolysosomes was analyzed (4.3±0.6 vs 7.2±0.8, respectively, P=0.0088).
Conclusions: C-kit+ stem cells preserve podocyte cytoskeleton in a model of PAN-induced glomerulonephritis apparently by up-regulating the mTOR-Rictor pathway and modulating the autophagic pathway. Taken together, these results suggest that c-kit+ stem cells may have important biological and therapeutic properties.
- © 2013 by American Heart Association, Inc.