Notch signaling in the collecting duct regulates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in mice

BACKGROUND/AIMS: Mind bomb-1 (Mib1) encodes an E3 ubiquitin ligase, which is required for the initiation of Notch signaling. Recently, it was demonstrated that the renal collecting duct plays an important role in renal fibrosis. Here, we investigated the role of Notch signaling in renal fibrosis using conditional knockout mice with the specific ablation of Mib1 in renal collecting duct principal cells. METHODS: Mib1-floxed mice (Mib1f/f ) were crossed with aquaporin 2 (AQP2)-Cre mice in order to generate principal cell-specific Mib1 knockout mice (Mib1f/f :AQP2-Cre+). Unilateral ureteral obstruction (UUO) was performed, and mice were sacrificed 7 days after UUO. RESULTS: After performing the UUO, renal tubulointerstitial fibrosis and the expression of transforming growth factor β were markedly enhanced in the obstructed kidneys of Mib1f/f mice compared with the sham-operated kidney of Mib1f/f mice. These changes were shown to be even more pronounced in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in those of the Mib1f/f mice . Furthermore, the number of TUNNEL-positive cells in renal collecting duct was higher in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in the kidneys of Mib1f/f mice. CONCLUSIONS: Notch signaling in the renal collecting duct plays an important role in the regulation of renal tubulointerstitial fibrosis and apoptosis after UUO.

Renal Expression of Ammonia Transporters in Rats with Amiloride-Induced Renal Tubular Acidosis / 대한내과학회지

BACKGROUND/AIMS: Renal tubular acidosis (RTA) decreases the net acid excretion, predominantly due to a decrease in urinary ammonia excretion. This study examined whether this decrement is associated with changes in the renal expression of the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg), in rats with amiloride-induced RTA. METHODS: Male Sprague-Dawley rats were treated intraperitoneally with amiloride (3 mg/kg/day) for 6 days. Rhbg and Rhcg expression was evaluated by immunoblotting and immunohistochemistry. Cell height, total cellular expression, expression in the apical 25% of the cell, and apical expression as a percentage of total expression were quantified using immunohistochemistry with quantitative morphometric analysis. RESULTS: After amiloride treatment for 6 days, the serum bicarbonate level was decreased, and serum potassium was increased. The total urinary ammonia excretion and potassium excretion were decreased. The total Rhbg and Rhcg protein expression levels were not changed in the cortex or outer medulla of the kidney. Light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated that total Rhcg expression was decreased in the cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) in amiloride-induced RTA, whereas Rhbg immunoreactivity was unchanged. CONCLUSIONS: Rats with amiloride-induced RTA have decreased urinary ammonia excretion associated with decreased Rhcg expression in the CCD and OMCD, suggesting that the ammonia transporter Rhcg plays an important role in the pathogenesis of amiloride-induced RTA.

Carcinoma renal dos ductos de Bellini / Bellini duct carcinoma of the Kidney

Two types primary epithelial tumours of the kidney have been distinguished, such as renal cell carcinoma (hypernephroma or Grawitz) deriving from proximal tubules and carcinoma arising in the urothelium of the kidney's collecting system. Mancilla-Jimenez e cols were the first to describe in 1976 an atypical papillary carcinoma of the kidney deriving from collecting duct system-Bellini duct carcinoma (BDC). In the World Healthy Organization classification it is listed as a rare carcinoma ( 1 percent of the renal malignancies) originating in the renal medulla. Histologic examination shows both tubular and papillary architeture, which can lead to misinterpretation as renal cell or transitional cell carcinoma. Renal cell carcinoma originates from the metanephrogenic blastema and collecting duct carcinoma derived embryologicaly from the mesonephron Wolff duct. Renal cell carcinoma has been shown to express both cytokeratins and vimetin, whereas the distal convoluted tubule expresses only cytokeratins. BDC can be considered as a renal malignancy with a very bad prognosis compared to the other renal cell carcinoma. The best treatment is radical nephrectomy. A case of BDC is reported in a young black man, 27 year old with only history of light left back pain. Ultrasound and other image examinations showed a tumour about 6 cm in the middle and low left kidney. Patient was submitted to extraperitoneal radical nephectomy. Microscopic evaluation revealed kidney's collecting duct carcinoma with metastasis on two retroperitoneal lymphy nodes.