Jaeseok Yang

Seoul National University Hospital, Sŏul, Seoul, South Korea

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Publications (54)141.62 Total impact

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    ABSTRACT: Diagnosing acute rejection (AR) in kidney transplant recipients typically requires an invasive kidney biopsy. A previous study has suggested that expression of five genes in peripheral blood can indicate the presence of AR in American pediatric kidney transplant recipients. This study aims to validate if these five genes are also useful to diagnose AR in Korean adult kidney transplant patients.
    Transplantation 09/2014; · 3.78 Impact Factor
  • Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 09/2014; · 2.21 Impact Factor
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    ABSTRACT: Asian patients undergoing kidney transplantation (KT) generally have better renal allograft survival and a lower burden of cardiovascular disease than those of other racial groups. The KNOW-KT aims to explore allograft survival rate, cardiovascular events, and metabolic profiles and to elucidate the risk factors in Korean KT patients.
    BMC Nephrology 05/2014; 15(1):77. · 1.64 Impact Factor
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    ABSTRACT: The role of hyperuricemia in disease progression of autosomal dominant polycystic kidney disease (ADPKD) has not been defined well. We investigated the association of serum uric acid (sUA) with renal function and the effect of hypouricemic treatment on the rate of renal function decline. This is a single-center, retrospective, observational cohort study. A total of 365 patients with ADPKD who had estimated glomerular filtration rate (eGFR) >= 15 mL/min/1.73 m2 and who were followed up for > 1 year were included in our analysis. Hyperuricemia was defined by a sUA level of >= 7.0 mg/dL in male and >= 6.0 mg/dL in female or when hypouricemic medications were prescribed. Hyperuricemia was associated with reduced initial eGFR, independent of age, sex, hypertension, albuminuria, and total kidney volume. During a median follow-up period of over 6 years, patients with hyperuricemia showed a faster annual decline in eGFR (-6.3% per year vs. -0.9% per year, p = 0.008). However, after adjusting for age, sex, hypertension and initial eGFR, sUA was no longer associated with either annual eGFR decline or the development of ESRD. Among 53 patients who received hypouricemic treatment, the annual eGFR decline appeared to be attenuated after hypouricemic treatment (pretreatment vs. posttreatment: -5.3 +/- 8. 2 vs. 0.2 +/- 6.2 mL/min/1.73 m2 per year, p = 0.001 by Wilcoxon signed-rank test). Although hyperuricemia was associated with reduced eGFR, it was not an independent factor for renal progression in ADPKD. However, the correction of hyperuricemia may attenuate renal function decline in some patients with mild renal insufficiency.
    BMC Nephrology 04/2014; 15(1):63. · 1.64 Impact Factor
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    ABSTRACT: We performed a retrospective cohort study to determine the prognostic value of standard criteria donor/expanded criteria donor (SCD/ECD) designation, with regard to one-yr GFR and graft survival rate, in a region with short, cold ischemic time (CIT), and how this designation compares with the kidney donor risk index (KDRI) and zero-time kidney biopsies. We reviewed 362 cases of deceased donor kidney transplantation (DDKT). Donor kidneys were classified as SCD or ECD. They were also assessed by the KDRI. Zero-time kidney biopsy was performed in 196 patients, and histologic score was assessed. Median follow-up duration was 46 months. Forty-two cases (11.6%) used ECD kidneys. The mean CIT was only 4.9 ± 2.7 h. Graft survival rates were not significantly different between ECD and SCD groups. The KDRI showed the best correlation with one-yr estimations of glomerular filtration rate (eGFR) (R(2) = 0.230, p < 0.001), and higher KDRI was associated with a higher risk of graft failure (hazard ratio 2.63, 95% confidence interval 1.01-6.87). However, higher histologic score was not associated with a higher risk of graft failure. KDRI has greater predictive value for short-term outcomes in DDKT with short CIT than the SCD/ECD designation or pathology.
    Clinical Transplantation 02/2014; · 1.63 Impact Factor
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    ABSTRACT: Generation of transgenic pigs for xenotransplantation is one of the most promising technologies for resolving organ shortages. Human heme oxygenase-1 (hHO-1/HMOX1) can protect transplanted organs by its strong anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Soluble human TNFRI-Fc (shTNFRI-Fc) can inhibit the binding of human TNF-α (hTNF-α) to TNF receptors on porcine cells, and thereby, prevent hTNF-α-mediated inflammation and apoptosis. Herein, we successfully generated shTNFRI-Fc-F2A-HA-hHO-1 transgenic (TG) pigs expressing both shTNFRI-Fc and hemagglutinin-tagged-human heme oxygenase-1 (HA-hHO-1) by using an F2A self-cleaving peptide. shTNFRI-Fc and HA-hHO-1 transgenes containing the F2A peptide were constructed under the control of the CAG promoter. Transgene insertion and copy number in the genome of transgenic pigs was confirmed by polymerase chain reaction (PCR) and Southern blot analysis. Expressions of shTNFRI-Fc and HA-hHO-1 in TG pigs were confirmed using PCR, RT-PCR, western blot, ELISA, and immunohistochemistry. shTNFRI-Fc and HA-hHO-1 were expressed in various organs, including the heart, lung, and spleen. ELISA assays detected shTNFRI-Fc in the sera of TG pigs. For functional analysis, fibroblasts isolated from a shTNFRI-Fc-F2A-HA-hHO-1 TG pig (i.e., #14; 1 × 10(5) cells) were cultured with hTNF-α (20 ng/mL) and cycloheximide (10 μg/mL). The viability of shTNFRI-Fc-F2A-HA-hHO-1 TG pig fibroblasts was significantly higher than that of the wild type (wild type vs. shTNFRI-Fc-F2A-HA-hHO-1 TG at 24 h, 31.6 ± 3.2 vs. 60.4 ± 8.3 %, respectively; p < 0.05). Caspase-3/-7 activity of the shTNFRI-Fc-F2A-HA-hHO-1 TG pig fibroblasts was lower than that of the wild type pig fibroblasts (wild type vs. shTNFRI-Fc-F2A-HA-hHO-1 TG at 12 h, 812,452 ± 113,078 RLU vs. 88,240 ± 10,438 RLU, respectively; p < 0.05). These results show that shTNFRI-Fc and HA-hHO-1 TG pigs generated by the F2A self-cleaving peptide express both shTNFRI-Fc and HA-hHO-1 molecules, which provides protection against oxidative and inflammatory injury. Utilization of the F2A self-cleaving peptide is a promising tool for generating multiple TG pigs for xenotransplantation.
    Transgenic Research 02/2014; · 2.61 Impact Factor
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    ABSTRACT: Background Highly sensitized (HS) patients seldom have chance to receive kidney transplant. To increase transplantation rate among those population, previous IV immunoglobulin and rituximab desensitization protocol showed good transplant conversion rate, but also carried moderate rate of antibody mediated rejection. Bortezomib, a proteasome inhibitor can control the production of anti-HLA antibodies through plasma cell apoptosis. A single center waitlist desensitization program was employed to facilitate successful kidney transplantation in HS patients group. Methods We prospectively enrolled 23 patients from Jul 2010 to Dec 2013. Desensitization protocol included two doses of IVIG (2 g/kg), single dose of rituximab (375 mg/m2, max 500 mg), and 4 days of bortezomib (1.3 mg/m2 on days 1,3,7 and 9). Anti-HLA class I and II antibodies were determined by Luminex solid phase bead assay at baseline and M2, M3 and M6. We investigated the difference of transplant conversion rate between desensitized HS patients and non-desensitized HS waitlist patients. Also we analyzed the difference of PRA % values and mean fluorescence intensity (MFI) between pre- and post-desensitization serum. Results Mean age of treatment group was 48.7±11.2 years old. Male to female ratio was 12:11. O+ blood type patients were 34.8% of patients. Mean duration of previous renal replacement therapy were 153.5±65.5 months. Baseline mean class I and II PRA % values were 86±15.3 and 66±34. Baseline class I and II MFI values were 13,893±6,147 and 12,274±6,891. After desensitization, kidney transplant were successfully performed in 34.8% of patients, compared to 13.8% transplant conversion rate among non-desentized HS controls (p=0.001 by Log-Rank). Among KT recipients, median duration of waiting after desensitization was 3 months with interquartile range 2-8.1 months. Class I PRA % had showed decreased values until 3 months after desensitization. After 6 months, there were no differences between the class I PRA values between pre-desensitization samples and post-desensitization samples. There were no other differences except class I PRA % values. Desensitization protocol were generally well tolerated, with the completion rate of 92% patients. There were no serious adverse events, but moderate adverse event were in 46%, most commonly fever and diarrhea. Conclusion Highly sensitized waitlist patients are manageable by desensitization protocol including bortezomib.
    Kidney Research and Clinical Practice. 01/2014; 33(2):A2.
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    ABSTRACT: BK virus-associated nephropathy (BKVAN) is one of the major causes of allograft dysfunction in kidney transplant (KT) patients. We compared BKVAN combined with acute rejection (BKVAN/AR) with BKVAN alone in KT patients. We retrospectively analyzed biopsy-proven BKVAN in KT patients from 2000 to 2011 at Seoul National University Hospital. Among 414 biopsies from 951 patients, biopsy-proven BKVAN was found in 14 patients. Nine patients had BKVAN alone, while 5 patients had both BKVAN and acute cellular rejection. BKVAN in the BKVAN alone group was detected later than in BKVAN/AR group (21.77 vs 6.39 months after transplantation, P=0.03). Serum creatinine at diagnosis was similar (2.09 vs 2.00 mg/dL). Histological grade was more advanced in the BKVAN/AR group (P=0.034). Serum load of BKV, dose of immunosuppressants, and tacrolimus level showed a higher tendency in the BKVAN alone group; however it was not statistically significant. After anti-rejection therapy, immunosuppression was reduced in the BKVAN/AR group. Renal functional deterioration over 1 yr after BKVAN diagnosis was similar between the two groups (P=0.665). These findings suggest that the prognosis of BKVAN/AR after anti-rejection therapy followed by anti-BKV therapy might be similar to that of BKVAN alone after anti-BKV therapy.
    Journal of Korean medical science 12/2013; 28(12):1711-5. · 0.84 Impact Factor
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    ABSTRACT: The organ shortage is as serious in Korea as in other parts of the world. As about one-third of the potential living donors are ABO incompatible (ABOi), transplantation across the blood group barrier can help overcome this shortage. One hundred and twenty-five ABOi kidney transplantations (KTs) were performed between 2007 and 2010 in Korea. We collected the perioperative and follow-up data for 118 of these patients until September 2011. The preconditioning and immunosuppressive protocols were almost identical across the different transplant centers, with rituximab but no splenectomy; pre-transplant plasmapheresis (PP) with target anti-A/B titer 8 or 16 on transplant day, on-demand, rather than routine, post-transplant PP, and tacrolimus-based immunosuppressants. The number of patients and participating centers showed a rapid increase over time, and in 2010, ABOi KT (n = 79) comprised 10% of all the living donor KTs in Korea. The mean follow-up period was 21 months (range, 1-56 months). Sixteen (14%) patients developed acute rejection, and three of these had antibody-mediated rejection (AMR). Two-yr patient and graft survival were 99.2% and 97.5%, respectively. No graft was lost due to AMR. ABOi KT is rapidly expanding in Korea with excellent medium-term outcome and will help mitigate the organ shortage.
    Clinical Transplantation 10/2013; · 1.63 Impact Factor
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    ABSTRACT: Chronic antibody-mediated rejection (CAMR) in renal transplant patients has poor allograft outcomes. However, treatment strategy has not been established yet. Herein, we present short-term outcomes of combination therapy for CAMR. We identified 9 patients with CAMR or suspicious CAMR who were treated with antihumoral therapy from 2010 to 2011 and analyzed their medical records retrospectively. Five patients had CAMR, and 4 patients had suspicious CAMR. Severe transplant glomerulopathy (TG) was observed in 7 patients. The estimated glomerular filtration rate (eGFR) was decreased in all patients before treatment. We used 3 different treatment regimens: (1) high-dose intravenous immunoglobulin (IVIG) and rituximab; (2) high-dose IVIG, rituximab, and bortezomib; and (3) plasmapheresis with low-dose IVIG, rituximab and bortezomib. After treatment with 1 of these 3 regimens, graft function improved or stabilized in 6 patients, whereas 3 patients showed further deterioration of eGFR. The third regimen suppressed deterioration of renal function in all patients. Most patients showed no progression of proteinuria. Infectious complications due Pneumocystis jirovecii pneumonia and herpes zoster occurred in 2 patients. Combination therapy for CAMR might be effective, even in patients with relatively late-stage CAMR.
    Nephrology 09/2013; · 1.69 Impact Factor
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    ABSTRACT: Regulatory T cells (Tregs) can suppress immunologic damage in renal ischemia-reperfusion injury (IRI), but the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate renal IRI in mice. IL-2C administered before bilateral renal IRI induced Treg expansion in both spleen and kidney, improved renal function, and attenuated histologic renal injury and apoptosis after IRI. Furthermore, IL-2C administration reduced the expression of inflammatory cytokines and attenuated the infiltration of neutrophils and macrophages in renal tissue. Depletion of Tregs with anti-CD25 antibodies abrogated the beneficial effects of IL-2C. However, IL-2C-mediated renal protection was not dependent on either IL-10 or TGF-β. Notably, IL-2C administered after IRI also enhanced Treg expansion in spleen and kidney, increased tubular cell proliferation, improved renal function, and reduced renal fibrosis. In conclusion, these results indicate that IL-2C-induced Treg expansion attenuates acute renal damage and improves renal recovery in vivo, suggesting that IL-2C may be a therapeutic strategy for renal IRI.
    Journal of the American Society of Nephrology 07/2013; · 8.99 Impact Factor
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    ABSTRACT: INTRODUCTION: Neural stem cells (NSCs) are among the most promising candidates for cell replacement therapy in neuronal injury and neurodegenerative diseases. One of the remaining obstacles for NSCs therapy is to overcome the alloimmune response on NSCs by the host. METHODS: To investigate the mechanisms of immune modulatory function derived from the interaction of human NSCs with allogeneic T cells, we examined the immune regulatory effects of human NSCs on allogeneic T cells in vitro. RESULTS: Significantly, NSCs induced apoptosis of allogeneic T cells, in particular CD4+ T cells. Interaction of CD70 on NSCs and CD27 on CD4+ T cells mediated apoptosis of T cells. Thus, blocking CD70-CD27 interaction prevented NSCs-mediated death of CD4+ T cells. CONCLUSIONS: Here we present a rational explanation of NSCs-induced immune escape in two consecutive stages. First, CD70 constitutively expressed on NSCs engaged CD27 on CD4+ T cells, which induced FasL expression on CD4+ T cells. Second, CD4+ T cell apoptosis was followed by Fas-FasL interaction in the CD4+ T cells.
    Stem Cell Research & Therapy 05/2013; 4(3):56. · 3.65 Impact Factor
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    ABSTRACT: Retransplantation is common in allogeneic islet transplantation, and therefore, memory responses in previously sensitized recipients present a distinct obstacle for successful islet transplantation. Given the difficulties in controlling memory responses contributing to allograft rejection, it is worth investigating the effects of new immune-modulating agents against islet allograft rejection in the sensitized recipients. In this study, we investigated immune-modulating agents including 5-azacytidine and IL-2/anti-IL-2 complex to ascertain their suppressive effects on memory responses. In suppression assays, rapamycin effectively suppressed the proliferation of memory T cells, whereas 5-azacytidine, a methylation inhibitor suppressed the survival and proliferation of memory T cells. Combination therapy of anti-CD40L, anti-OX40L, and rapamycin slightly prolonged BALB/c islet allograft survival in sensitized C57BL6 mice, and reduced intragraft infiltration of macrophages, T cells, and B cells. However, the addition of IL-2/anti-IL-2 complex, an inducer of regulatory T cells, did not exhibit additional suppression against rejection in sensitized mice. Although a combination of 5-azacytidine and rapamycin markedly suppressed islet allograft rejection in naïve mice, it failed to achieve long-term graft survival even when combined with anti-CD40L and anti-OX40 in sensitized mice. In short, 5-azacytidine-based or IL-2/anti-IL-2 complex-based regimens can suppress islet allograft rejection in naïve recipients, but fail to control islet allograft rejection in sensitized recipients.
    Transplant Immunology 01/2013; · 1.52 Impact Factor
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    ABSTRACT: BACKGROUND: Urinary tract infection (UTI) occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD). However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown. METHODS: We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined. RESULTS: With a mean follow-up duration of 65.3 months, 176 (68.8%) out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01) and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension). The annual change in estimated glomerular filtration rate ([increment]eGFR) was significantly larger in magnitude in group B than in group A (-2.7+/-4.56 vs. -1.17+/-5.8, respectively; P=0.01). Age and Group B found to be the independent variables for [increment]eGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001). CONCLUSIONS: Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.
    BMC Nephrology 01/2013; 14(1):1. · 1.64 Impact Factor
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    ABSTRACT: In pig-to-primate xenotransplantation, multiple transgenic pigs are required to overcome a series of transplant rejections. The generation of multiple transgenic pigs either by breeding or the introduction of several mono-cistronic vectors has been hampered by the differential expression patterns of the target genes. To achieve simultaneous expression of multiple genes, a poly-cistronic expression system using the 2A peptide derived from the Thosea asigna virus (T2A) can be considered an alternative choice. Before applying T2A expression system to pig generation, the expression patterns of multiple genes in this system should be precisely evaluated. In this study, we constructed several bi-cistronic T2A expression vectors, which combine target genes that are frequently used in the xenotransplantation field, and introduced them into porcine fibroblasts. The proteins targeted to the same or different subcellular regions were efficiently expressed without affecting the localization or expression levels of the other protein. However, when a gene with low expression efficiency was inserted into the upstream region of the T2A sequences, the expression level of the downstream gene was significantly decreased compared with the expression efficiency without the insertion. A small interfering RNA targeting one gene in this system resulted in the significant downregulation of both the target gene and the other gene, indicating that multiple genes combined into a T2A expression vector can be considered as a single gene in terms of transcription and translation. In summary, the efficient expression of a downstream gene can be achieved if the expression of the upstream gene is efficient.
    PLoS ONE 01/2013; 8(7):e70486. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND:: Wide variation in tacrolimus concentrations and low tacrolimus exposure have been reported to be associated with poor renal graft outcomes in non-Asians. The CYP3A5 polymorphism is a representative genetic factor that might affect this association, together with environmental factors. We investigated whether tacrolimus variability or the mean tacrolimus trough concentration can influence kidney allograft outcomes in Asians and whether the CYP3A5 polymorphism (rs776746) can affect this relationship. METHODS:: Data from renal transplant patients between 2000 and 2010 were analyzed retrospectively. The tacrolimus intraindividual variability (IIV) and the mean tacrolimus trough concentration were calculated from the tacrolimus concentrations between 6 and 12 months after transplantation. RESULTS:: A total of 249 renal transplant patients were enrolled. The patients with higher tacrolimus IIV had shorter rejection-free survival (P = 0.002). However, there was no difference in rejection-free survival between CYP3A5 expressers and nonexpressers. The tacrolimus IIV was not associated with the CYP3A5 polymorphism. High IIV of tacrolimus was an independent risk factor of biopsy-proven acute rejection after adjusting for mean tacrolimus concentration, HLA mismatch, induction therapy, donor type, and CYP3A5 polymorphism (hazard ratio 2.655, 95% confidence interval 1.394-5.056). Interestingly, the impact of tacrolimus IIV on acute rejection was significant in CYP3A5 expressers, whereas it was not in CYP3A5 nonexpressers. CONCLUSIONS:: The IIV of tacrolimus trough concentrations had a significant impact on rejection-free survival. The effect was influenced by CYP3A5 polymorphism, although the tacrolimus variability itself was not determined by the CYP3A5 polymorphism.
    Therapeutic drug monitoring 12/2012; 34(6):680-685. · 2.43 Impact Factor
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    ABSTRACT: BACKGROUND: Toll-like receptors (TLRs) are involved in the rejection of solid organ allografts. However, the roles of TLRs in islets are still controversial. We investigated the roles of TLRs in donor islets together with those in recipients in allogeneic islet transplantation. METHODS: To assess the roles of TLRs in either donor islets or recipients, allogeneic islet transplantation was performed using myeloid differentiation factor 88 (MyD88)-knockout (KO), TLR4-KO, or Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)-KO mice. RESULTS: Both polyriboinosinic polyribocytidylic acid and lipopolysaccharide (LPS) stimulation induced the mRNA expression of regulated and normal T cell expressed and secreted, interferon-γ-inducible protein-10, monocyte chemotactic protein-1, interleukin-8, and inducible nitric oxide synthase in murine islets, whereas the induction was attenuated in TRIF-KO, interferon-β promoter stimulator-1-KO, and TLR4-KO mice. When islets from MyD88-KO, TLR4-KO, or TRIF-KO C57BL/6 mice were transplanted to BALB/c recipients, graft survival was not better than that of wild-type (WT) islets. However, the survival of the MyD88-KO islet allograft was significantly prolonged when combined with anti-CD40L. In parallel, LPS stimulation in donor islets interfered with anti-CD40L blockade-mediated long-term survival of islet allografts in TLR4-KO recipients. LPS stimulation increased the perigraft infiltration of both T cells and macrophages. Then again, when islets from WT BALB/c mice were transplanted to MyD88-KO, TRIF-KO, or WT C57BL/6 mice, there was no difference in graft survival, although some of the MyD88-KO recipients obtained long-term graft survival. However, anti-CD40L prolonged graft survival significantly in MyD88-KO recipients. The absence of MyD88 in either donors or recipients decreased the perigraft infiltration of inflammatory cells when combined with anti-CD40L. CONCLUSIONS: TLRs in both donor islets and recipients are involved in islet allograft rejection.
    Transplantation 11/2012; 94(10):1005-1012. · 3.78 Impact Factor
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    ABSTRACT: BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells has been regarded as an early mechanism of peritoneal fibrosis. A substantial and rapidly growing literature indicates that HO-1 provides the provenance for pathways that can interrupt virtually all major mechanisms of tissue injury. The effects of HO-1 expression on EMT, which plays a critical role in the development of peritoneal membrane (PM) fibrosis, are unknown and its roles in peritoneal fibrosis has not been studied, yet. METHODS: A piece of human omentum obtained from consenting patients undergoing elective abdominal surgery was used for study. We treated the human peritoneal mesothelial cells (HPMCs) with high glucose solution and HO-1 inducer (hemin, 10 μmol/L). To further investigate the pure effect of HO-1 on EMT of mesothelium, gene transfer of recombinant Adenovirus-harboring human HO-1 (Adv-HO-1 gene) to HPMCs was done. RESULTS: Exposure of HPMCs to HG solution resulted in an increase of the expression of mesenchymal markers such as α-smooth muscle actin (α-SMA) and was associated with a decrease in the expression of epithelial markers, E-cadherin. HO-1 protein expression was decreased in the same situation. Treatment of HPMCs with HO-1 inducer, hemin showed a dosage-dependent amelioration of HG induced changes in markers of EMT with increase of expression of HO-1. Human HO-1 gene transfection resulted in a significant increase in HO-1 expression and ameliorated HG-induced changes in expression of E-cadherin and α-SMA. CONCLUSION: Taken together, our results suggest that HO-1 has a critical role in the modulation of peritoneal fibrosis, and, more important, the suppression of EMT. This study is the first to show the beneficial effect of HO-1 on reversing EMT in MC.
    Clinical and Experimental Nephrology 11/2012; · 1.25 Impact Factor
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    ABSTRACT: Although innate immunity plays important roles in xenograft rejection, there have been few studies on the role of toll-like receptors (TLRs) in xenotransplantation. Furthermore, most studies focused on the recipient's TLRs. Therefore, we investigated whether TLRs in porcine islets can contribute to islet xenograft rejection. Adult porcine islets were isolated and stimulated by polyinosinic:polycytidylic acid (Poly I:C) or lipopolysaccharide (LPS). Both Poly I:C and LPS stimulation in porcine islets induced expression of chemokines (RANTES, MCP-1, IP-10, and IL-8), cytokines (IL-6 and type I interferons), and adhesion molecules (VCAM-1 and ICAM-1). Porcine islet supernatants stimulated by TLR agonists induced chemotaxis of human leukocytes. They also induced procoagulant activation (tissue factor and fgl-2). However, TLR stimulation did not influence insulin secretion. When porcine MyD88 was knocked-down using shRNA lentivirus, TLR-mediated induction of proinflammatory mediators and procoagulants was attenuated. When LPS was injected to MyD88 or TLR4 knockout mice after porcine islet transplantation, LPS stimulation on donor islets interfered with islet xenograft tolerance induction by anti-CD154 antibodies. Inflammatory cell infiltration and expression of proinflammatory chemokines and cytokines in islet xenografts also increased. In conclusion, TLR activation in porcine islets induced both a proinflammatory and procoagulant response, and thereby contributed to xenograft rejection.
    Cell Transplantation 10/2012; · 4.42 Impact Factor
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    ABSTRACT: We performed retrospective, multi-center study of the impacts of parathyroidectomy (PTX) after or before kidney transplantation on allograft outcomes. A total of 63 patients who underwent PTX after kidney transplantation were identified. Deterioration in eGFR by more than 25% at 1 month after PTX occurred in 20% of the patients. The baseline eGFR was significantly lower in impairment group than nonimpairment group [adjusted odds ratio (OR) 0.87, 95% confidence interval (CI) 0.77-0.99, P = 0.033]. Low iPTH concentration after PTX was also a significant risk factor for the renal impairment (OR 0.96, CI 0.94-0.99, P = 0.009). A total of 37 patients who underwent PTX before transplantation were identified. Thirty-six percent of the patients had persistent hyperparathyroidism by 1 year after transplantation. A high iPTH level before PTX was a significant risk factor for persistent post-transplant hyperparathyroidism (adjusted OR 1.002, CI 1.000-1.005, P = 0.039). Finally, eGFR values during the first 5 years after transplantation were significantly lower in the patients who underwent PTX at less than 1 year after transplantation, than the pretransplant PTX patients (P = 0.032). As PTX after kidney transplantation has a risk of deterioration of allograft function, pretransplant PTX should be considered for patients with severe hyperparathyroidism, who could undergo post-transplant PTX.
    Transplant International 09/2012; · 3.16 Impact Factor

Publication Stats

179 Citations
141.62 Total Impact Points

Institutions

  • 2003–2014
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2003–2012
    • Seoul National University
      • • College of Medicine
      • • Department of Internal Medicine
      • • Division of Nephrology
      Seoul, Seoul, South Korea
  • 2009–2010
    • Eulji University
      • Department of Internal Medicine
      Taiden, Daejeon, South Korea
  • 2007–2010
    • Gachon University
      • Department of Internal Medicine
      Seoul, Seoul, South Korea
    • University of Incheon
      Sŏul, Seoul, South Korea