RESULTS: Exposure of HK2 cells to HG (60 mM) resulted in an increase of the expression of fibronectin and vimentin, and was associated with a decrease in the expression of E-cadherin. Treatment of HK2 cells with SFN showed an amelioration of HGinduced changes in EMT markers with an increase of Nrf2-HO-1 expression. We found that SFN protects experimental diabetic nephropathy, at least in part, via inhibition of PI3K-AKT-GSK-3b signaling pathway. We observed SFN inhibited HG-induced generation of reactive oxygen species (ROS), phosphorylation of PI3K-AKT at serine 473, and phosphorylation inhibition of serine/threonine kinase glycogen synthase kinase-3b (GSK-3b) at serine 9. These signaling resulted in the down-regulation of Snail transcriptional factor and recovery of E-cadherin.

INTRODUCTION AND AIMS: The coenzyme nicotinamide adenine dinucleotide (NADþ) plays a crucial role in regulation of redox status and energy metabolism under stress. It has been reported that NADþ treatment can attenuate brain and cardiac ischemia-reperfusion injury (I/R) injury. However, whether it has beneficial effects on renal I/R injury remains unknown. In the present study, we assessed the therapeutic effects of NADþ in renal I/R injury and tried to investigate the potential mechanism.

Introduction and Aims: Acute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI).In severe cases, AIN may progress to chronic kidney disease or end-stage renal disease.We previously reported that WNT10A is a novel angio/ stromagenic factor in wound healing and organ fibrosis.In this study, we investigated the role of WNT10A in fibrotic progression of AIN.Methods: Kidney biopsy specimens from 25 AKI patients (all men, ≥60 years) treated in our hospital between 2007 and 2013 were examined for WNT proteins, α-SMA, and fibronectin expression by immunohistochemistry.The relationship between each WNT proteins expression level and estimated glomerular filtration rate (eGFR) was evaluated by the Mann-Whitney U test.COS1 cells (kidney fibroblasts from African green monkey) were transfected with a WNT10A expression plasmid or a siRNA targeting peroxiredoxin 5 (PRDX5).The effects of WNT10A overexpression and PRDX5 knockdown on proliferation and hydrogen peroxide induced cytotoxicity were measured by WST-8 assay.Results: The 10 patients exhibiting WNT10A expression in biopsy tissue had significantly lower eGFR values (median, 11.12 mL/min per 1.73 m 2 ; range, 7.16-28.15mL/min per 1.73 m 2 ) than the 15 patients exhibiting no detectable WNT10A expression (34.70, 8.37-134.58;p = 0.0033).There was no significant relationship between eGFR and the expression level of any other WNT protein examined (WNT-1, -3, and -4).Overexpression of WNT10A in COS1 cells enhanced proliferation, fibronectin expression, PRDX5 expression, and resistance to hydrogen peroxide, while PRDX5 downregulation sensitized COS1 cells to hydrogen peroxide.Conclusions: WNT10A expression may promote fibrotic progression and kidney dysfunction in AIN.Blockade of WNT10A expression may be a feasible therapeutic strategy against kidney fibrosis.

The Department of Pathology and Laboratory Medicine offers a Ph.D. in Biomedical Sciences with a focus on Experimental Pathology. The graduate program emphasizes experimental approaches to better understand the molecular and cellular mechanisms of disease, particularly human disease. Principal areas of research investigated by faculty in Experimental Pathology include concentrating studies in microbial genomics, innate immunity, cellular stress, stem cell biology, developmental neurobiology, cancer, and neurodegenerative disease. The Department of Pathology & Laboratory Medicine offers a graduate program in Experimental Pathology. Application to Experimental Pathology is generally through one of two "gateway" programs, which offer multidisciplinary graduate training under the heading of Cellular and Molecular Biosciences (CMB) (https://cmb.uci.edu) or the Interdepartmental Neuroscience Program (INP) (https://inp.uci.edu). Members of the Pathology faculty participate in the CMB and INP programs. The CMB and INP programs include a first-year curriculum and the opportunity to rotate through two or more research laboratories. For the CMB program, students select a specific area of interest from ten areas of academic study, one of which is Experimental Pathology. Experimental Pathology emphasizes experimental approaches to better understand the molecular and cellular mechanisms of disease, with a focus on human disease. After the first year in the CMB or INP program, students interested in Experimental Pathology will join the laboratories of faculty within the department or the laboratories of approved affiliated faculty. Students end of third year. The normative time for completion of the Ph.D. is five years, and the maximum time permitted is seven years. immune evasion by cancer, diseases mediated by cytokine dysregulation, role of the microbiome of the GI tract and other disease sites, and adoptive T-cell therapy.

Introduction and Aims: Clinical studies have demonstrated the risk of chronic kidney disease after the occurrence of an acute kidney injury (AKI).Experimental works indicate that AKI result in incomplete repair, persistent tubulointerstitial inflammation and fibrosis.Cysteine-rich protein 61 (Cyr61), a secreted matrix-associated protein, has been found to be up-regulated in the kidney ischemia reperfusion injury (IRI) animal model.The present study aimed to investigate the role of Cyr61 in the kidney after IRI.Methods: Using mouse unilateral IRI model, we analyzed gene and protein expression of Cyr61.We further investigated the effect of blockade of Cyr61 in unilateral IRI mice by treating polyclonal anti-Cyr61 antibody or non-specific IgG.In addition, we used proximal tubular epithelial (NRK-52E) cells for cell culture studies.Results: After IRI, kidney Cyr61 expression increased significantly in both mRNA and protein level.Immunofluorescence staining indicated Cyr61 was predominantly expressed in renal proximal tubular epithelial cells.This was supported by in vitro studies showing hypoxia condition stimulate Cyr61 expression in NRK-52E cells.Daily treatment with anti-Cyr61 antibody produced a decrease in the renal type 1 collagen, PAI-1, MCP-1, and IL-1 gene expression, as well as α-SMA protein production at day 14 after IRI.The degree of collagen fibril accumulation, evaluated by picrosirius red staining, and macrophage infiltration were both attenuated by the Cyr61 blockade on day 7 and 14.Concurrently, renal VEGF-A gene expression was enhanced and vessel density was more preserved at day 14 in the treatment group.Conclusions: Renal Cyr61 expression by tubular epithelial cells is enhanced after IRI.Our findings suggest that Cyr61 contributes to the renal inflammation, vascular rarefaction, and fibrosis after ischemic AKI.