In our unpublished meta-analysis, we searched PubMed using the key words ‘birthweight’, ‘intrauterine growth retardation’, ‘intrauterine growth restriction’, ‘creatinine clearance’, ‘glomerular filtration rate’ and ‘renal function’; five studies which observed 2733 subjects aged 18 years or older were included, and we found that

GFR of LBW people was approximately 3 mL/min per 1.73 m2 lower than that of normal counterparts (Fig. 1). One study compared the birthweight between 1230 end-stage renal disease (ESRD) patients and 2460 healthy controls and revealed that birthweight less than 2.5 kg or higher than 4.0 kg was associated with the highest ESRD risk ZD1839 and birthweight between 3.5–4.0 kg was associated with the lowest ESRD risk.34

Whereas another matched case–control study did not reveal the association between birthweight and ESRD in a population of 1162 subjects.35 A longitudinal study with a duration of 38 years observed over 2 million people, and results showed that BKM120 LBW people had 1.5 times higher risk of ESRD. However, in this study, ESRD mainly occurred before the age of 14 years old, which was possibly due to the higher incidence of congenital or inherited renal disease in the LBW population.36 In a study on the familial aggregation of ESRD, LBW was not an influence factor but high birthweight was considered as a protective factor.37 Three meta-analyses showed that birthweight was negatively associated with blood pressure in different age stages, with every 1 kg increase of birthweight resulting in a 1.2–2 mmHg decrease of blood pressure,38–40 possibly Dichloromethane dehalogenase resulting from kidney hyperfiltration caused by glomerulosclerosis and damage of renal sodium excretion capacity. The risk of diabetes and dyslipidaemia was also higher in LBW people.41,42 This could be explained by their susceptibility to obesity and insulin resistance and their special growth process, namely,

malnutrition in uterine, relative over-nutrition after birth and excessive fast growth in the early stage of life.43 LBW also influenced the structure and function of the cardiovascular system,44 such as the damage of vessel dilation function and the turbulence of endo-epithelial function. It is a reasonable speculation that this kind of abnormality could also exist in the capillary of nephrons and the function of glomerular endothelium. LBW also influences sympathetic nerve45 and renin–angiotensin system activity.46 Some researchers owed the higher risk of CKD in certain races such as black people47 and goajiro Indians48 to their higher LBW mortality. However, one study revealed that low nephron number and LBW may play a role in the development of hypertension in white subjects but not in black.49 Another study showed that the more severe hypertension found in black subjects could not be attributed to racial differences in number of glomeruli or birthweight.

fumigatus infection, which suggests that IFN-β is a possible adjuvant to elicit an appropriate Th reactivity to A. fumigatus. Dendritic cells were prepared as previously described.9 CD14+ monocytes were cultured with 25 ng/ml granulocyte–macrophage colony-stimulating factor (GM-CSF; Schering-Plough, Levallois Perret, France) and 1000 U/ml IL-4 (R&D Systems, Minneapolis, MN) for 5 days. On day 5, about 90% of the cells express CD1a+ and 95% express

CD14−. The DCs were starved from IL-4 and GM-CSF for 20 hr before infection or treatments. Monoclonal antibodies specific for CD1a, CD14, CD38, CD40, CD83, CD86, HLA-DR, CD3 and CD4 as well as immunoglobulin G1 (IgG1), IgG2a HM781-36B cost and IgG2b (BD Bioscience PharMingen, San Diego, CA) were

used as direct conjugates to fluorescein isothiocyanate (FITC) or phycoerythrin. Lipopolysaccharide (LPS) from Escherichia coli 0111:B4 (Sigma-Aldrich, St Louis, MO) was used at a concentration of 100 ng/ml to stimulate DC maturation and IFN-β expression. The IFN-β (Avonex®; Biogen Inc., Cambridge, MA) was used at 200 pm. A wild-type clinical isolate of A. fumigatus (CBS 144 89) was grown on Sabouraud–chloramphenicol agar for 3 days, at 37°, as previously described.23 Preparations of A. fumigatus were analysed for LPS contamination by the Limulus lysate assay (Biowhittaker, Verviers, Belgium) and were found to contain less than PF 2341066 10 pg/ml LPS. In all experiments, DCs were infected with live A. fumigatus conidia at a 1 : 1 ratio. Amphotericin B (0·75 μg/ml; Sigma-Aldrich) was added to the cell

cultures to prevent fungal overgrowth 6 hr after infection when the internalization of A. fumigatus conidia was completed.9 For the adherence assay, A. fumigatus conidia were incubated with FITC at a final concentration of 3 mg/ml overnight at 4°, and then washed extensively with PBS. After a 6-hr incubation with FITC-labelled Adenosine triphosphate conidia (ratio 1 : 1), DCs were washed and the adherence was measured by flow cytometric analysis. The cells were incubated with purified monoclonal antibodies at 4° for 30 min. After washing, the cells were fixed with 2% paraformaldehyde before analysis on a FACScan using the cellquest software (BD Bioscience PharMingen). A total of 5000 cells were analysed per sample. RNA extraction, reverse transcription (RT) and real-time RT-polymerase chain reaction (PCR) assays were performed as previously described.24 Sequences of the primer pairs used for glyceraldehyde 3-phosphate dehydrogenase (GaPDH), IFN-β, IL-12p35, IL-23p19 and IL-27p28 quantification were previously described.24 Cytokine concentration in filtered supernatants was evaluated with the human inflammation cytometric bead array (CBA) [for IL-12p70, IL-10, tumour necrosis factor-α (TNF-α) and IL-6: BD Bioscience PharMingen] and enzyme-linked immunsorbent assay (ELISA; for IFN-β: PBL Biomedical Laboratories, Piscataway, NJ; for IL-23: eBioscience, San Diego, CA).

Alternatively, it is also possible that the concentration ranges of both antagonists are not within the optimal concentration window to affect LPS-induced MCP-1 and IL-6, an assumption further supporting the ligand-concentration-dependent regulation of chemokines and cytokines by CGRP receptor signalling. It can be generalized here that CGRP receptor signalling, in a ligand-concentration-dependent manner, exerts either stimulating or inhibiting effects on basal and LPS-induced release of pro-inflammatory

and anti-inflammatory chemokines and cytokines. Ligand-concentration-dependent modulation of chemokine and cytokine Selleck Target Selective Inhibitor Library by CGRP receptor signalling is probably a novel mechanism underlying the pro-inflammatory and anti-inflammatory properties of CGRP receptor signalling in immune and inflammatory responses. In the present study, we observed that LPS concentration- and time- dependently induced the production of CGRP from RAW macrophages. The LPS-induced NGF, IL-1β, IL-6, PGE2 and NF-κB signalling

facilitates this event whereas NGF trkA receptor and CGRP RAMP1 exert a negative feedback on the release of CGRP. These results PLX4032 suggest a fine-tune regulation of CGRP production in macrophages by other inflammatory Carnitine palmitoyltransferase II mediators during immune and inflammatory responses. On the other hand, through autocrine or paracrine pathways, CGRP receptor signalling can either promote or inhibit the production of pro- and anti-inflammatory chemokines and cytokines in macrophages. The ligand-concentration-dependent modulation of inflammatory mediators by CGRP receptor signalling is a novel mechanism underlying the pro- and anti-immune and inflammatory roles of CGRP. Taken together, these data demonstrate that monocytes/macrophages are an important source of CGRP, which has a reciprocal effect on the production

of pro- and anti-inflammatory mediators. This study was supported by grants from Canadian Institutes of Health Research to Weiya Ma and Remi Quirion. F. Vercauteren is the recipient of a FRSQ postdoctoral fellowship. The authors declare no conflict of interest. “
“Human bone marrow-derived mesenchymal stem cells (MSC) are multipotent non-hematopoietic progenitors that have regulatory activity on immune cells. NOD- and Toll-like receptors (NLR, TLR) have several roles in immunity, including those relevant to pathogen recognition and shaping the course of immune responses by controlling gene expression. We have shown that these innate immune receptors are expressed by hematopoietic CD34+ progenitors and MSC.

Although Cav1 is associated with certain bacterial infections, it is unknown whether Cav1 is involved in host immunity against Klebsiella pneumoniae, the third most commonly isolated microorganism from

bacterial sepsis patients. Here, we showed that cav1 knockout mice succumbed to K. pneumoniae infection with markedly decreased survival rates, increased bacterial Cell Cycle inhibitor burdens, intensified tissue injury, hyperactive proinflammatory cytokines, and systemic bacterial dissemination as compared with WT mice. Knocking down Cav1 by a dominant negative approach in lung epithelial MLE-12 cells resulted in similar outcomes (decreased bacterial clearance and increased proinflammatory cytokine production). Furthermore, we revealed that STAT5 influences the GSK3β−β-catenin−Akt pathway, which contributes to the intensive inflammatory response and rapid infection dissemination seen in Cav1 deficiency. Collectively, our findings indicate that Cav1 may offer resistance to K. pneumoniae infection, by affecting both systemic and local production of proinflammatory cytokines via the actions of STAT5 and the GSK3β−β-catenin−Akt pathway. Caveolae Erlotinib price are flask-shaped lipid microdomains in the plasma membrane. As part of an alternative pathway to receptor-mediated endocytosis, caveolae are involved in various cellular activities such as lipid storage, phagocytosis, small molecule uptake, and secretion [[1]]. A recent addition

to this list is a potential role in pathogenic infections. Escherichia coli, for example, relies on caveolae to invade both phagocytic and nonphagocytic cells [[2]]. Caveolae are composed of lipids and proteins. A major scaffold protein for these structures is Caveolin-1 (Cav1), which is expressed at high Farnesyltransferase levels in endothelial and epithelial cells. Cav1 has been shown to be biologically important, having been shown to be involved in uptake of the Simian Virus-40 [[3]] and the BK virus [[4]]. Wang et al. [[5]] also demonstrated that Cav1 inhibits HIV-1 envelope-induced apoptosis

through interactions with gp41 in CD4+ T lymphocytes. Furthermore, Cav1 is involved in uptake of not only viral pathogens but also larger bacterial pathogens [[6]]. Knockout (KO) mouse studies have revealed multi-faceted roles for Cav1 in infectious diseases [[7]]. Malik et al. [[7]] found that cav1 KO mice exhibited decreased mortality due to decreased levels of inflammation mediated by interactions with nitric oxide. In contrast, cav1 KO mice with Salmonella typhimurium infection showed increased inflammatory cytokine levels and mortality [[8]]. Gadjeva et al. [[9]] showed that Cav1 is essential for host defense against Pseudomonas aeruginosa as cav1 KO mice manifested a typical phenotype with decreased bacterial clearance and more severe infection. However, another study suggested that Cav1 is not involved in P. aeruginosa invasion in the lung [[10]].

The remaining LP were incubated twice for 25 min at 37°C in RPMI medium containing DNAse (5 mg), collagenase A (25 mg), collagenase D (25 mg), dispase I (0.3 g) and penicillin/streptomycin (100 U/mL). Lymphocytes were then collected, passed though the cell strainer and resuspended in medium. Single-cell suspensions prepared from different organs of recipient mice were stained and analyzed on FACSCalibur or FACSCanto (Becton Dickinson, Mountain View, CA) using FlowJo software (Tree Star). For surface phenotyping of lymphocyte populations, the following fluorochrome-conjugated

or biotinylated mAbs were used: anti-CD4 (RM4-5), Saracatinib research buy anti-CD25 (PC61), anti-CD3 (145-2C11) and anti-γδ TCR (GL-3) (eBioscience or BD Bioscience). For determination of intracellular cytokine production, cells were restimulated with PMA (20 ng/mL), ionomycin (1 nM) for 4 h at 37°C in the presence of BD GolgiStop™ (1:1000 dilution). Cells were then stained for surface antigens, fixed/permeabilized with Fix/Perm solution (eBioscience) and stained with anti-IFN-γ (XMG1.2), anti-IL-17A (TC11-18H10.1 or eBio17B7), anti-IL-10 (JES5-16E3), anti-IL-2 (JES6-5H4) (purchased from eBioscience or BD Bioscience). In order to determine cellular see more proliferation in vivo, cells were stained intracellularly with anti-Ki-67 (B56)

(BD Bioscience), as described above. Colons were collected in RNAlater (Qiagen, Mississauga, ON) and frozen at −20°C until use. RNA was extracted following the TRIzol protocol (Invitrogen, Burlington, ON). Total RNA was reverse-transcribed using the cDNA Archive Kit (Applied Biosystems, Foster City, CA). Quantitative real-time PCR was performed using an ABI Prism 7900HT Sequence Detection System (Applied Biosystems) (1 PCR cycle, 95°C, 10 min; 40 PCR cycles, 60°C, 1 min, 95°C, 15 s). cDNA (10 ng total RNA) was

amplified in a reaction mix containing TaqMan Universal PCR Master Mix (Applied Biosystems) and corresponding TaqMan Gene Expression Assays (Applied Biosystems). Signals were analyzed by the ABI Prism Sequence Detection System software version lambrolizumab 2.2 (Applied Biosystems). The comparative Ct method for relative quantification was used, whereby all threshold cycles were normalized to the expression of 18s rRNA. Cytokine expression is represented as a fold-change relative to control non-diseased mice adoptively transferred with total CD4+ T cells. For suppression assay, FACS-sorted γδ TCR+ or CD4+CD25− T cells (50×103) were plated in 96-well, flat-bottomed microtiter plates (0.2 mL) with 200×103 irradiated total splenocytes and activated with soluble anti-CD3 (1 μg/mL) and IL-2 (100 U/mL). After 12 h, 75% of the medium was subtracted from each well, and FACS-sorted CD4+CD25+ TREG cells were added with fresh medium to the co-culture at various ratios. Cells were cultured for a total of 72 h at 37°C and pulsed for the last 12 h with 0.5 uCi of 3H-thymidine to determine the extent of proliferation.

In the absence of CXCL4 about 54.8±2.9% of the monocytes became apoptotic (AV+) and 15.7±4.9% CB-839 necrotic (AV+/PI+), while CXCL4-treated monocytes were efficiently protected against cell death (7.5±1.9% apoptotic and 6.1±2.4% necrotic cells; Fig. 3B). The anti-apoptotic effect of CXCL4 was only marginally affected by SKI at 1 μM (9.6±2.0% apoptotic and 9.8±4.3% necrotic cells), while in the presence of 3, 9 or 27 μM inhibitor statistically significant enhancement of cell death was observed (14.1±2.9%,

19.6±3.1%, or 36.8±5.0% apoptotic, and 11.7±2.3%, 15.9±4.4%, or 22.6±3.8% necrotic cells, respectively) as compared with controls cultured in the absence of SKI. It should be mentioned here that in the presence of D-erythro-N,N-dimethyl-sphingosine (DMS) (a more unspecific SKI) CXCL4-stimulated ROS formation is also inhibited dose-dependently, and CXCL4-mediated anti-apoptotic effect is reverted as observed in SKI-treated cells. By contrast to SKI, DMS pretreatment of unstimulated cells also results in decreased ROS formation, and increased cell death (data not shown). These data indicate that CXCL4-mediated protection from apoptosis is controlled by SphK. In a recent report we have demonstrated that several cytokines and chemokines were induced in CXCL4-treated monocytes CP-690550 nmr 3. To examine whether cytokine/chemokine expression is also regulated

by SphK, monocytes were preincubated in the presence Methane monooxygenase or absence of a constant dosage of SKI (9 μM). Subsequently, the cells were stimulated with 4 μM CXCL4 for 4 and 24 h. After 4 h, total RNA was isolated, transcribed into cDNA and gene expression was tested by RQ-PCR, and after 24 h cytokine/chemokine release was determined in cell culture supernatants. Preincubation of the cells with SKI resulted in a total block of CXCL4-induced increase of CCL2, IL-6, and TNF mRNA (Fig. 3C, left panels), and release of the corresponding

proteins was strongly reduced (Fig. 3C, right panels). From these data we conclude that SphK activity is required for CXCL4-stimulated cytokine/chemokine expression. To strengthen our results with SKI, we next used siRNA knockdown strategy to verify these data. ROS production induced by CXCL4 has been shown in monocytes as well as in macrophages 2. Since for technical reasons monocytes could not be used for knockdown experiments, GM-CSF-generated macrophages were used instead. Preincubation of macrophages with SKI or DMS (9 μM each) resulted in a strong and significant reduction (83 and 96%, respectively) of CXCL4-induced ROS formation (data not shown). More importantly, treatment of macrophages with SphK1-specific siRNA resulted in 33% decreased SphK1 mRNA expression and 41% reduction in CXCL4-mediated ROS production after 24 h (Fig. 3D). To better understand by which mechanisms CXCL4-activated SphK1 regulates monocyte survival, we investigated the role of caspases in this process.

Antibiotics can clear most infections and have a benefit for individual patients, but because of the large number of infected people and the increasing resistance to antibiotics, a more realistic

approach is the development of a vaccine. Granted that some experts doubt the possibility of making a protective H. pylori vaccine because the natural infection persists despite the host developing a strong immune response (Blanchard & Czinn, 2000). Yet, the fact that a postinfection immune response is not able to clear an infection does not necessarily negate the possibility that preinfection immunity may prevent the acquisition of a new infection. In fact, experimental animal selleck kinase inhibitor data suggest that oral administration of Helicobacter-specific antibodies may be effective to prevent as well as to treat Helicobacter infection (Czinn et al., 1993; Casswall et al., 2002; Gorell & Robins-Browne, 2009). For 20 years, a number of researchers have been working toward the development of a vaccine to prevent H. pylori infection (Czinn & Nedrud, 1991). Of the various candidate antigens, the most promising is the B subunit of the urease protein (urease B), a 65-kDa protein encoded in a 1.7-kbp gene. The protein, which is exposed on the selleck surface of the cell membrane, frequently

elicits an immune response (Futagami et al., 1998), and its activity (likely by counteracting the gastric acidity) is crucial for the survival of this bacterium, as shown by the fact that urease-deficient H. pylori mutants fail to colonize the gastric mucosa (Eaton et al., 1991). Ferrero et al. (1994) reported that 4��8C immunization with urease B resulted in 25–60% protection against Helicobacter felis (the Helicobacter species that naturally infects mice) challenge, as compared with no protection with urease A. Subsequent work has shown that mice immunized with whole-cell lysate or urease B purified protein (either natural or recombinant) results in protection against infection following challenge with either H. pylori SS1 (an H. pylori strain adapted

to colonize mice) (Kleanthous et al., 1998) or H. felis (Chen et al., 1992; Michetti et al., 1994). Despite these progresses, a vaccine for H. pylori remains elusive. Immunization of mice results in a reduction but rarely an elimination of Helicobacter organisms in the stomach (Sutton et al., 2000) and the few attempts to immunize human volunteers have not resulted in adequate immunogenicity (Kreiss et al., 1996; Michetti et al., 1999; Kotloff et al., 2001). Therefore, even though urease B remains an attractive candidate, its immunogenicity has to be improved. To achieve this goal, researchers have experimented with various strong adjuvants (such as Freund’s, cholera toxin or Escherichia coli labile toxin), but due to their toxicity, they have no human application.

In this study, we examined tubulointerstitial nestin expression in human glomerulonephritis. Methods:  Renal biopsy specimens obtained from 41 adult patients with immunoglobulin (Ig)A nephropathy were studied. Nestin expression was determined by immunohistochemical staining and estimated by digital image analysis. To identify the phenotype of nestin-positive cells, a double immunofluorescent study was performed for nestin and CD34 (a marker for endothelial cells) or α-smooth muscle actin (α-SMA, a marker for myofibroblasts). Results:  In normal

kidney, nestin expression was restricted LY294002 solubility dmso to the podocytes and was not detected in tubular cells and tubulointerstitial cells. In contrast, increased nestin expression was observed at tubulointerstitial areas of IgA nephropathy. The degree of tubulointerstitial nestin expression was positively correlated with tubulointerstitial fibrosis (r = 0.546, P < 0.001). The double immunofluorescent study showed check details that most nestin-positive cells in the interstitium were co-stained

with CD34 or α-SMA, suggesting that peritubular endothelial cells and tubulointerstitial myofibroblasts express nestin during the progression of tubulointerstitial injury. In addition, strong nestin expression was associated with deterioration of renal function. Conclusion:  Nestin expression is associated with tubulointerstitial Ketotifen injury and predicts renal prognosis in IgA nephropathy. Nestin could be a new marker for peritubular endothelial cell injury and tubulointerstitial fibrosis. “
“Aim:  The slit diaphragm (SD) of podocyte impairment contributes to massive proteinuria and progressive glomerulosclerosis in many human glomerular diseases.

The aim of the study was to determine if thiazolidinedione (TZD) reduce proteinuria and glomerulosclerosis in focal segmental glomerulosclerosis (FSGS) by preserving the structure and function of SD. Methods:  Adriamycin-induced FSGS rat models were employed. Urinary protein content was measured dynamically during the experiment. Additional biochemical parameters in serum samples were measured after the animals were killed. Glomerular sclerosis index (SI) and podocyte foot processes fusion rate (PFR) were evaluated. The protein and mRNA expressing levels of nephrin, podocin and CD2-associated protein (CD2AP) in glomeruli were assessed by immunohistochemistry and real-time quantitative polymerase chain reaction, respectively. The density of podocytes was also evaluated after anti-Wilms’ tumour-1 immunohistochemical staining. Results:  Rosiglitazone treatment partially reduced proteinuria, but did not significantly affect the serum levels of triglyceride, cholesterol, albumin, glucose, urea nitrogen and creatinine in Adriamycin-induced FSGS rats. Glomerular SI and podocyte foot PFR were significantly attenuated by rosiglitazone treatment.

This notion, however, has not been tested by randomized controlled trials. The aim of the Imatinib cell line present study was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in IgAN. Methods: This multicenter

study was conducted between April 1, 2005 and March 31, 2010 in 18 university or community hospitals located in major cities across Japan. Patients with biopsy-proven IgAN, proteinuria of 1.0–3.5 g/day and serum creatinine equal to or less than 1.5 mg/dl were randomly allocated to tonsillectomy combined with steroid pulses (Group A) or steroid pulses alone (Group B). The primary endpoints were the rate of change in urinary protein excretion during 12 months of the observation period, and the frequency of the disappearance of proteinuria and/or haematuria

after 12 months. The secondary endpoints were a change in eGFR from baseline, the frequencies of a 100% increase in serum creatinine from baseline, a 50% decrease in eGFR from baseline, indications for renal replacement therapy, and adverse effects. Selleckchem Autophagy inhibitor Data were subjected to intension-to-treat analysis. Multivariate logistic regression analyses

were also performed to examine the impact of tonsillectomy, renal function, blood pressure, urinary protein excretion and the use of rennin-angiotensin system (RAS) inhibitors at baseline on achieving the disappearance of proteinuria, haematuria or both at study completion. Results: Eighty patients were enrolled, and 40 were allocated to each group. Seven and one patients in Group A Thiamet G and Group B, respectively, were found not meet inclusion criteria or withdrew consent. During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than Group B (mixed effects model, p < 0.05). Although the frequency of the disappearance of proteinuria after 12 months was also higher in Group A (63%) compared to Group B (39%), the difference did not show the statistical significance (p = 0.052). The frequency of the disappearance of haematuria or both proteinuria and haematuria was not significantly different between Group A and Group B (68% vs 64%, and 47% vs 28%, respectively).

However, there is marked regional variation in the uptake of home haemodialysis (HD) and peritoneal dialysis (PD) suggesting further scope for the expansion of these modalities. Methods:  Between 1 April and 5 August 2009, Australian nephrologists were invited to complete an online survey. Seventy-six questions were Idasanutlin asked covering characteristics of the dialysis units, responders’ experience, adequacy of facilities and support structures, attitudes to the use of home HD and PD and issues impeding the increased uptake of home dialysis. Results:  Completed surveys were received and analysed from 71 respondents; 27 from Heads of Units (35% response rate) and 44 (16%) from other nephrologists. There was strong agreement

that HD with long hours was advantageous

and that this was most easily accomplished in the home. PD was not considered to be an inferior therapy. A ‘PD first’ policy existed in 34% of Renal Units. The most commonly reported impediments to expanding home dialysis services were financial disadvantage for home HD patients, and lack of physical infrastructure for training, support and education. Areas of concern for expanding home dialysis programmes included psychiatry support, access to respite care and home visits, and lack of support from medical administration and government. The majority of nephrologists would recommend home dialysis to more patients if these impediments could be overcome. Conclusion:  This survey identified support from nephrologists for the expansion of home dialysis in Australia and highlighted important barriers to improving access to these therapies. “
“Aim:  Bortezomib ic50 Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death or proliferation. Unilateral

ureteral obstruction (UUO) is a model of progressive renal fibrosis in the obstructed kidney. And UUO is followed by compensatory cellular proliferation in the contralateral kidney. We investigate the role of autophagy PRKD3 in the obstructed kidney and contralateral kidney after UUO. Methods:  To obtain the evidence and the patterns of autophagy during UUO, the rats were sacrificed 3, 7 and 14 days after UUO. To examine the efficacy of the autophagy inhibitors, 3-methyladenine (3-MA), the rats were treated daily with intraperitoneal injection of 3-MA (30 mg/kg per day) for 7 days. Results:  After UUO, autophagy was induced in the obstructed kidney in a time-dependent manner. Inhibition of autophagy by 3-MA enhanced tubular cell apoptosis and tubulointerstitial fibrosis in the obstructed kidney after UUO. In the contralateral kidney, autophagy was also induced and prolonged during UUO. Inhibition of autophagy by 3-MA increased the protein expression of proliferating cell nuclear antigen significantly in the contralateral kidney after UUO. The Akt-mammalian target of rapamycin (mTOR) signalling pathway was involved in the induction of autophagy after UUO in both kidneys.