TGF-β Mediated Epithelial-Mesenchymal Transition in Autosomal Dominant Polycystic Kidney Disease

Purpose: Recent studies have showed that epithelial-mesen-chymal transition (EMT) is a key process of glomerular and tubulointerstitial pathology in many chronic kidney diseases. However, there are no data of EMT in humane autosomal dominant polycystic kidney disease (ADPKD). Patients and Methods: ADPKD kidneys (N = 5) with end stage renal disease (ESRD) and control kidneys (N = 4) were analyzed immnunohistochemically. We evaluated α-SMA, E-cadherin, vimentin, TGF-β1 and Smad 2/3 expression in ADPKD and compared them with those in control kidney. These immuno-histochemical findings were quantitatively analyzed by com-puter-assisted image analyzer and positive tubules (%). Results: There were severe interstitial fibrosis and prolifera-tion of α-SMA+ myofibroblasts in ADPKD. Cystic tubular epithelial cells in ADPKD lost epithelial marker (E-cadherin) and expressed mesenchymal markers (α-SMA, vimentin). There were significant increases of α-SMA (34.3 ± 11.7 % vs 0.9 ± 1.5%), vimentin (19.9 ± 3.9 % vs 3.3 ± 1.4%), TGF-β1 (5.42 ± 2.83 % vs 0%) and Smad 2/3 (3.4 ± 1.7 % vs 0.7 ± 0.6%) in ADPKD kidneys compared with control kidneys evidenced by computer-assisted image analyzer. When we analyze the posi-tive tubules (%), the results were the same as computer-assisted image analyzer. Conclusion: Our results showed that the end stage of ADPKD is associated with TGF-β, Smad 2/3 and markers of EMT. It suggests that TGF-β mediated EMT has a role in progression of ADPKD. Key Words: Epithelial mesenchymal transition, antosomal dominant polycystic kidney diseas

Development of a Perirenal Hematoma after Hula-Hooping

The development of a perirenal hematoma is rare and primarily the result of trauma, malignancy, or a connective tissue disease. Infrequently, a continuous or even mild trauma can cause a perirenal hematoma. Here, we report a case involving the development of a perirenal hematoma after excessive hula-hooping in the absence of a major trauma history

The Ability of β-Cells to Compensate for Insulin Resistance is Restored with a Reduction in Excess Growth Hormone in Korean Acromegalic Patients

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and β-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naïve acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and β-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and β-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI0,120) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI0,120 and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and β-cell function are improved by tumor resection in acromegalic patients

The Effects of Antidepressant Treatment on Serum Cytokines and Nutritional Status in Hemodialysis Patients

The aim of this study was to investigate the effects of antidepressant treatment on serum cytokines and nutritional status in hemodialysis patients. Twenty-eight hemodialysis patients with a depressed mood were given 20 mg of fluoxetine for 8 weeks. The degree of depressive symptoms, the serum levels of interleukin-1β, interleukin-2, interleukin-6, tumor necrosis factor-α, c-reactive protein, and markers of nutritional status were assessed at baseline and after treatment. The outcome was assessed in terms of response to treatment (>50% reduction in the score of the Hamilton depression rating scale). Antidepressant treatment decreased the serum level of interleukin-1β in both response and nonresponse groups, and increased the serum level of interleukin-6 only in the response group. At baseline, the level of interleukin-6 in the response group was lower than in the nonresponse group. Antidepressant treatment also increased fat distribution significantly in the response group which might have slightly improved the nutritional status. This study suggests that antidepressant treatment improve depressive symptoms and may affect immunological functions and nutritional status in chronic hemodialysis patients with depression

Polycystin-1 Expression in Fetal, Adult and Autosomal Dominant Polycystic Kidney

The mutation of the PKD1 gene causes autosomal dominant polycystic kidney disease (ADPKD), and the PKD1 gene encodes polycystin-1 (PC-1). PC-1 is thought to be a cell-cell/matrix adhesion receptor molecule at the cell surface that is widely expressed in the kidney. However, there are controversies about the role of PC-1 protein and its expression when using different antibodies to detect it. We used two PC-1 antibodies; C-20 (Santa Cruz, sc-10372) as the C-terminal antibody, and P-15 (Santa Cruz, sc-10307) as the N-terminal antibody. We evaluated the PC-1 expression by performing immunoblotting on the human embryonic kidney (HEK) 293 cells and the renal proximal tubular epithelial cell (RPTEC) lysates. We characterized the expression of PC-1 in the fetal, adult and polycystic kidneys tissues by performing immunohistochemistry. We confirmed the PC-1 expression in the HEK 293 cells and the RPTEC lysates, but the expression was very low. The PC-1 proteins were diffusely expressed in the tubular epithelial cells cytoplasm in the fetal and adult kidneys, and the PC-1 expression was more prominent in the proximal tubules of the fetal kidney. In the ADPKD kidney, the PC-1 proteins were heterogenously and weakly expressed in the tubular or cyst lining epithelial cells. Our data suggests that the development of the kidney may regulate the expression of PC-1, and an altered PC-1 expression may contribute to cyst formation in ADPKD