Background: Endoplasmic reticulum (ER) stress induced by urinary albumin plays an important role in tubulointerstitial injury. We have shown that albumin-induced ER stress is regulated through reactive oxygen species (ROS)-c-Src kinase-mTOR signaling pathways. We postulated that peroxisome proliferator-activated receptor-γ (PPAR-γ) might also act as an upstream signaling molecule between c-Src kinase and mTOR. It has been suggested that AMP-activated protein kinase (AMPK) is involved in attenuation of ER stress. We examined whether and how activation of AMPK suppressed the albumin-induced ER stress and apoptosis in tubular epithelial cells. Method: HK-2 cells, a proximal tubular cell line, were used. Protein expressions were measured by Western blot analysis. Intracellular ROS and apoptosis were analyzed by flow cytometry. Results: Albumin-induced PPAR-γ expression and PPAR-γ inhibitor (GW9662) suppressed the albumin-induced ER stress. c-Src kinase inhibitor and GW9662 reduced the albumin-induced PPAR-γ and mTOR, respectively. Metformin (the best known clinical activator of AMPK) and another AMPK activator (AICAR) suppressed the albumin-induced ER stress via inhibition of ROS through induction of endogenous antioxidant thioredoxin. AMPK inhibitor blocked the effect of metformin and AICAR. Our in vivo animal study showed that metformin reduced the renal cortical expression of ER stress protein (GRP78) in protein-overload proteinuria rats. Metformin also reducedthe caspase 3-dependent apoptosis induced by albumin. Conclusion: PPAR-γ was involved in albumin-induced ER stress as an upstream signaling molecule between c-Src kinase and mTOR. AMPK activation might be beneficial in attenuating the tubulointerstitial injury induced by albumin.

Background. Epithelial-to-mesenchymal transition (EMT) is thought to play a significant role in the advancement to chronic kidney disease and contributes to the deposition of extracellular matrix proteins and renal fibrosis relating to diabetic nephropathy. Method. We studied the effect of Nrf2-HO-1 signaling on high-glucose- (HG-) induced EMT in normal human tubular epithelial cells, that is, HK2 cells. In short, we treated HK2 cells with HG and sulforaphane (SFN) as an Nrf2 activator. EMT was evaluated by the expression activity of the epithelial marker E-cadherin and mesenchymal markers such as vimentin and fibronectin. Results. Exposure of HK2 cells to HG (60 mM) activated the expression of vimentin and fibronectin but decreased E-cadherin. Treatment of HK2 cells with SFN caused HG-induced attenuation in EMT markers with activated Nrf2-HO-1. We found that SFN decreased HG-induced production of reactive oxygen species (ROS), phosphorylation of PI3K/Akt at serine 473, and inhibitory phosphorylation of serine/threonine kinase glycogen synthase kinase-3β (GSK-3β) at serine 9. Subsequently, these signaling led to the downregulation of the Snail-1 transcriptional factor and the recovery of E-cadherin. Conclusion. The present study suggests that Nrf2-HO-1 signaling has an inhibitory role in the regulation of EMT through the modulation of ROS-mediated PI3K/Akt/GSK-3β activity, highlighting Nrf2-HO-1 and GSK-3β as potential therapeutic targets in diabetic nephropathy.

Background/Aims: Desmopressin decreases bleeding time in uremic patients. Although bleeding time is the most frequently used measure of global platelet function, this test has important disadvantages. In vitro closure time (CT) is a relatively new and efficient test of primary hemostasis. We designed a prospective randomized study to evaluate the effect of desmopressin on platelet function, as measured by in vitro CT, in uremic patients. Methods: Forty-eight uremic patients, about to commence hemodialysis and with prolonged CT, were randomized to infusion with desmopressin (n = 24) or saline alone (n = 24). Complete blood count, prothrombin time, activated partial thrombin time, levels of plasma fibrinogen, von Willebrand factor (VWF), factor VIII (FVIII) and CT were measured before and 1 h after desmopressin or saline infusion. Results: Following desmopressin infusion, collagen/epinephrine and collagen/adenosine diphosphate CT were significantly shortened from 212 ± 58 to 152 ± 45 s (p = 0.01) and from 189 ± 78 to 147 ± 58 s (p = 0.012), respectively; levels of FVIII and VWF were significantly increased from 188 ± 66 to 252 ± 93% (p = 0.017) and from 113 ± 9 to 121 ± 9% (p = 0.043), respectively. There were no significant changes in the control group. Conclusions: Desmopressin improved platelet dysfunction and increased the plasma concentrations of VWF and FVIII, suggesting that desmopressin may play a role in improving the bleeding tendency in uremic patients.

Korean red ginseng (KRG) has been traditionally used in Korea for health improvement. However, the clinical effect of KRG intake on the symptoms in patients with allergic rhinitis remains unknown. Our study was performed to identify the clinical effects of KRG on patients with allergic rhinitis and to examine the effect of KRG on allergic inflammatory reaction. We evaluated 60 patients with allergic rhinitis. All the patients were treated for 4 weeks. The patients were divided into 3 groups, according to the medication. Twenty patients were treated with KRG, 20 patients with the placebo, and 20 patients with the antihistamine. The patients recorded their symptoms in a daily symptom diary card. The patients checked the peak nasal inspiratory flow rate 2 times a day. Total serum immunoglobulin E (IgE) and serum-specific IgE were measured by ImmunoCap method before and after 4-week medication. The Th2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were checked in the serum before and after the 4-week treatment. The eosinophil counts in the nasal smears were checked. Korean red ginseng group has shown the significant improvement in rhinorrhea, nasal itching, and eye itching. Both the antihistamine and KRG groups showed a significant decrease in total IgE level at the end of treatment. The serum IL-4 level and eosinophil counts in the nasal smears were significantly decreased both in the antihistamine and in the KRG groups. In conclusion, KRG might be a useful treatment modality for patients with allergic rhinitis.