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1.
Article in English | WPRIM | ID: wpr-875497

ABSTRACT

Background/Aims@#Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. @*Methods@#Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. @*Results@#LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. @*Conclusions@#LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

2.
Article in English | WPRIM | ID: wpr-875472

ABSTRACT

Background/Aims@#We investigated whether serum neutrophil gelatinase-associated lipocalin (NGAL) can predict mortality in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). @*Methods@#This study enrolled 169 patients who underwent serum NGAL testing at CRRT initiation from June 2017 to January 2019. The predictive power of serum NGAL level for 28-day mortality was compared to the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score and Sequential Organ Failure Assessment (SOFA) score via area under the receiver operating characteristic curve (AuROC) value. @*Results@#There were 55 survivors and 114 non-survivors at 28 days post-CRRT initiation. Median serum NGAL level was significantly higher in the non-survivor group than in the survivor group (743.0 ng/mL vs. 504.0 ng/mL, p = 0.003). The AuROC value of serum NGAL level was 0.640, which was lower than APACHEII score and SOFA score values (0.767 and 0.715, respectively). However, in the low APACHE-II score group (< 27.5), AuROC value of serum NGAL was significantly increased (0.698), and it was an independent risk factor for 28 day-mortality (hazard ratio, 2.405; 95% confidence interval, 1.209 to 4.783; p = 0.012). @*Conclusions@#In patients with AKI requiring CRRT, serum NGAL levels may be useful for predicting short-term mortality in those with low APACHE-II scores.

3.
Article in English | WPRIM | ID: wpr-875448

ABSTRACT

Background/Aims@#To investigate if BK virus (BKV)-specific T cell immunity measured by an interferon-γ enzyme-linked immunospot (ELISPOT) assay can predict the outcome of BK virus infection in kidney transplant recipients (KTRs). @*Methods@#We included 68 KTRs with different viremia status (no viremia [n = 17], BK viremia [n = 27], and cleared viremia [n = 24]) and 44 healthy controls (HCs). The BK viremia group was divided into controller ( 3 months) according to sustained duration of BKV infection. We compared BKV-ELISPOT results against five BKV peptides (large tumor antigen [LT], St, VP1-3). @*Results@#BKV-ELISPOT results were higher in three KTRs groups with different BKV infection status than the HCs group (p < 0.05). In KTR groups, they were higher in cleared viremia group than no viremia or BK viremia group. Within the BK viremia group, controller group had higher LT-ELISPOT results compared to noncontroller group (p = 0.032). Also, KTRs without BK virus-associated nephropathy (BKVN) had higher LT, St, VP1, and VP2-ELISPOT results than those with BKVN (p < 0.05). @*Conclusions@#BKV-ELISPOT assay may be effective in predicting clinical outcomes of BKV infection in terms of clearance of BK virus and development of BKVN.

4.
Article | WPRIM | ID: wpr-831888

ABSTRACT

Background/Aims@#Coenzyme Q10 (CoQ10) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ10-based micelle formulation (CoQ10-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM). @*Methods@#We developed CoQ10-W from a glycyrrhizic-carnitine mixed layer CoQ10 micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ10 (CoQ10-L) or CoQ10-W for 4 weeks. Their plasma and pancreatic CoQ10 concentrations were measured using liquid chromatography- tandem mass spectrometry. The therapeutic efficacies of CoQ10-W and CoQ10-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells. @*Results@#The plasma CoQ10 level was significantly increased in the CoQ10-W group compared to that in the CoQ10-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ10-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ10-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ10-W but not by CoQ10-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ10-W than CoQ10-L. Electron microscopy revealed that CoQ10-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ10-L. In vitro studies showed that CoQ10-L and CoQ10-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent. @*Conclusions@#CoQ10-W has better therapeutic efficacy than CoQ10-L in TAC-induced DM.

5.
Article | WPRIM | ID: wpr-831827

ABSTRACT

Background/Aims@#It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. @*Methods@#We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. @*Results@#The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2’-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. @*Conclusions@#The nephrotoxic potential of HM containing AA was similar to that of AA itself.

6.
Article | WPRIM | ID: wpr-831760

ABSTRACT

Background/Aims@#Parathyroid hormone (PTH) is an important factor influencing immunologic dysfunction, but the effect of PTH level on infection-related outcomes remains unclear in incident dialysis. @*Methods@#We evaluated a multicenter prospective cohort study of 1,771 incident dialysis patients (1,260 hemodialysis and 511 peritoneal dialysis) in Korea. Patients were divided into three groups based on serum intact PTH (iPTH) level. The primary outcomes were all-cause and infection-related mortality and multivariate Cox regression analysis was performed to evaluate the role of iPTH in all-cause and infection-related mortality. @*Results@#During the follow-up period of 27.3 months, 175 patients (9.9%) died, and infection-related death represented 20% of all-cause mortality. Both all-cause mortality and infection-related mortality rates (p < 0.001 and p = 0.003, by logrank) were markedly higher in patients with serum iPTH < 150 pg/mL than in the other groups. Multivariate Cox regression analysis revealed that patients with serum iPTH < 150 pg/mL remained at higher risk for infection-related mortality than patients in the target range of 150 ≤ iPTH < 300 pg/mL, after adjusting for confounding variables (hazard ratio [HR], 2.52; 95% confidence interval, 1.06 to 5.99; p = 0.04). The HR of infection-related mortality in patients with serum iPTH < 150 pg/mL was significantly higher in patients with low serum phosphorus, low Ca × P product, low serum alkaline phosphatase and those older than 65 years. @*Conclusions@#Low serum iPTH level is an independent predictor of infection-related mortality in incident dialysis patients.

7.
Article | WPRIM | ID: wpr-831519

ABSTRACT

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.

8.
Article | WPRIM | ID: wpr-834934

ABSTRACT

Background@#The aim of this study was to compare the effect of anemia on clinical outcomes according to age in patients with end-stage renal disease (ESRD). @*Methods@#A total of 3,409 patients from the Clinical Research Center for ESRD were included and divided into three groups by age: age < 40 (n = 488), 40 ≤ age < 60 (n = 1,650), and age ≥ 60 (n = 1,271). We compared overall and cardiovascular mortality, and all-cause and cardiovascular hospitalization according to mean hemoglobin (Hb) concentration. @*Results@#Among participants ≥ 60 years of age, the Hb < 10 g/dL group had greater all-cause mortality (adjusted hazard ratio [HR], 2.098; 95% confidence interval [CI], 1.567-2.808; P < 0.001) than the 10 ≤ Hb < 12 g/dL group, whereas among participants < 40 years of age, the Hb ≥ 12 g/dL group had greater mortality than the 10 ≤ Hb < 12 g/dL group. Moreover, in participants ≥ 60 years of age, the HR for all-cause hospitalization for the Hb < 10 g/dL group was significantly greater than that of the 10 ≤ Hb < 12 g/dL group (HR, 1.472; 95% CI, 1.057-2.051; P = 0.022), whereas it was significantly lower in the Hb ≥ 12 g/dL group (HR, 0.544; 95% CI, 0.362-0.820; P = 0.004) However, among participants < 40 years of age, the incidence of all-cause hospitalization did not differ according to the Hb concentration (HR, 1.273; 95% CI, 0.814-1.991; P = 0.290 for the Hb < 10 g/dL group; reference, 10 ≤ Hb < 12 g/dL; HR, 0.787; 95% CI, 0.439-1.410; P = 0.265 for Hb ≥ 12 g/dL group). @*Conclusion@#The impact of anemia on mortality was more significant in elderly ESRD patients. Strict monitoring and management of anemia should be required for elderly ESRD patients.

9.
Article in English | WPRIM | ID: wpr-786195

ABSTRACT

BACKGROUND: Cancer rates are increasing not only in the general population but also in patients with end-stage renal disease. We investigated the changing pattern of pretransplant malignancy in kidney transplant recipients over 5 decades.METHODS: We reviewed 3,748 kidney transplant recipients between 1969 and 2016. We divided patients into three groups (1969–1998, 1999–2006, 2007–2016) based on the era of the cancer screening system used throughout the nation. We analyzed the incidence and pattern of pretransplant malignancy among the three groups. We also evaluated recurrent and de novo malignancy in these patients compared to patients without pretransplant malignancy.RESULTS: A total of 72 patients exhibited pretransplant malignancy (1.9%). There were no cases of pretransplant cancer until 1998, but the rate of pretransplant malignancy gradually increased to 1.1% during 1999–2006 and further increased to 4.3% thereafter. The most frequent types of pretransplant malignancy changed from the bladder, liver, and stomach cancers to thyroid cancer and renal cell carcinoma. There were no de novo cases, but there were three cases of recurrent cancer in patients with pretransplant malignancy; the recurrence rate among kidney transplant recipients with pretransplant malignancy was not significantly different from the incidence rate of de novo malignancy among kidney transplant recipients without pretransplant malignancy (4.2% vs. 6.9%, P = 0.48).CONCLUSION: The incidence of pretransplant malignancy in kidney transplantation candidates is gradually increasing, and recent increases were accompanied by changes in cancer types. Pretransplant malignancy may not be a hindrance to kidney transplantation because of the low incidence of posttransplant recurrence and de novo malignancy.


Subject(s)
Carcinoma, Renal Cell , Early Detection of Cancer , Humans , Incidence , Kidney Failure, Chronic , Kidney Transplantation , Kidney , Liver , Recurrence , Stomach Neoplasms , Thyroid Neoplasms , Transplant Recipients , Urinary Bladder
10.
Article in English | WPRIM | ID: wpr-759003

ABSTRACT

BACKGROUND: Hyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians’ perceptions regarding the diagnosis and management of AHU in CKD patients. METHODS: Questionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology. RESULTS: A total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serum uric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines). CONCLUSION: Most Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebro-cardiovascular complications.


Subject(s)
Cardiovascular Diseases , Diagnosis , Electronic Mail , Febuxostat , Female , Humans , Hyperuricemia , Male , Methods , Nephrology , Renal Insufficiency, Chronic , Surveys and Questionnaires , Uric Acid
11.
Article in English | WPRIM | ID: wpr-717186

ABSTRACT

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSIONS: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.


Subject(s)
Acute Kidney Injury , Adult , Chronic Disease , Diagnosis , Fanconi Syndrome , Female , Health Promotion , Herbal Medicine , Hospitalization , Humans , Incidence , Kidney Failure, Chronic , Korea , Medicine, East Asian Traditional , Medicine, Traditional , Nausea , Organization and Administration , Postpartum Period , Prognosis , United States Food and Drug Administration , Vomiting
12.
Article in English | WPRIM | ID: wpr-717054

ABSTRACT

BACKGROUND: Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non-HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients. METHODS: Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were retrospectively examined in 359 kidney transplant patients to determine the effect of each antibody on allograft survival and clinical characteristics. RESULTS: Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were detected in 37 (10.3%), 174 (48.5%), and 50 patients (13.9%), respectively. Post-transplant antibody-mediated rejection was associated with a pre-transplant HLA-DSA (+) status only. The development of microvascular inflammation (MVI) was associated with pre-transplant HLA-DSA (P=0.001) and anti-AT1R (P=0.036). Anti-AT1R (+) patients had significantly lower allograft survival compared with anti-AT1R (−) patients (P=0.042). Only pre-transplant anti-AT1R positivity was an independent risk factor for allograft failure (hazard ratio 4.824, confidence interval 1.017–24.888; P=0.038). MVI was the most common histological feature of allograft failure in patients with pre-transplant anti-AT1R. CONCLUSIONS: Pre-transplant anti-AT1R is an important risk factor for allograft failure, which may be mediated by MVI induction in the allograft tissue.


Subject(s)
Allografts , Angiotensin II , Angiotensins , Antibodies , Humans , Inflammation , Kidney Transplantation , Kidney , Major Histocompatibility Complex , Receptor, Angiotensin, Type 1 , Retrospective Studies , Risk Factors
13.
Article in Korean | WPRIM | ID: wpr-716932

ABSTRACT

BACKGROUND: Bortezomib has been used to treat antibody-mediated rejection (AMR) that usually develops after kidney transplantation (KT). Although it has been used in various clinical situations, it is difficult to precisely define how the drug affects the clinical course. We used bortezomib to treat eight cases of AMR that developed immediately following KT in patients who were resistant to conventional treatment. METHODS: Eight cases of refractory AMR that developed immediately after KT were treated with bortezomib on days 1, 4, 8, and 11. RESULTS: The resolution rate was 75%, and the 2-year rejection-free survival rate was 83%. Six cases underwent immunologically high-risk KT. Six recovering patients exhibited clinical improvement within 2 weeks of the first dose of bortezomib and recovered completely within 2 months. The effects of bortezomib seemed to be prolonged; only one additional rejection episode was observed. The two failed patients never exhibited any clinical improvement and progressed aggressively to graft failure soon after transplantation. Their donor specific anti-human leukocyte antigen antibody were sustained at high levels. CONCLUSIONS: Bortezomib is an effective rescue therapy in patients with AMR that developed immediately after KT.


Subject(s)
Bortezomib , Graft Rejection , Humans , Immunosuppression , Kidney Transplantation , Kidney , Leukocytes , Survival Rate , Tissue Donors , Transplants
14.
Article in English | WPRIM | ID: wpr-716638

ABSTRACT

Transplantation research has focused on cytotoxic T-cell and plasma cell/B-cell-targeted strategies, but little attention has been paid to the role of T helper 17 (Th17) cells in allograft dysfunction. However, accumulating evidence suggests that Th17 cells contribute to the development of acute and chronic allograft injury after transplantation of various organs, including the kidney. This review summarizes recent reports on the role of Th17 cells in kidney transplantation. Means of improving allograft outcomes by targeting the Th17 pathway are also suggested.


Subject(s)
Allografts , Kidney Transplantation , Kidney , Plasma , T-Lymphocytes , Th17 Cells
16.
Article in English | WPRIM | ID: wpr-716083

ABSTRACT

The establishment of protocols to differentiate kidney organoids from human pluripotent stem cells provides potential applications of kidney organoids in regenerative medicine. Modeling of renal diseases, drug screening, nephrotoxicity testing of compounds, and regenerative therapy are attractive applications. Although much progress still remains to be made in the development of kidney organoids, recent advances in clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated system 9 (Cas9) genome editing and three-dimensional bioprinting technologies have contributed to the application of kidney organoids in clinical fields. In this section, we review recent advances in the applications of kidney organoids to kidney disease modelling, drug screening, nephrotoxicity testing, and regenerative therapy.


Subject(s)
Bioprinting , Clustered Regularly Interspaced Short Palindromic Repeats , Drug Evaluation, Preclinical , Genome , Humans , Kidney Diseases , Kidney , Organoids , Pluripotent Stem Cells , Regenerative Medicine , Transplantation
17.
Article in English | WPRIM | ID: wpr-714802

ABSTRACT

Lymphoproliferative disorder in a posttransplant setting has emerged as a difficult problem in kidney transplantation (KT). Lymphoma involving adnexa of the eye has rarely been reported due to scarcity of lymphoreticular tissue in the ocular area. This report presents a case of a 37-year-old KT recipient who was diagnosed with conjunctival mucosa-associated lymphoid tissue lymphoma with a chief complaint of seeing black spots. Unlike other post-transplant lymphoproliferative diseases associated with the Epstein-Barr virus (EBV) reactivation via immunosuppression, the lesion was not related to the virus. The patient received radiotherapy with concomitant conversion from the tacrolimus to the sirolimus. Overall, the results presented herein indicate lymphoma may be an important differential diagnosis when KT recipients complain of ocular discomfort.


Subject(s)
Adult , Diagnosis, Differential , Herpesvirus 4, Human , Humans , Immunosuppression , Kidney Transplantation , Kidney , Lymphoid Tissue , Lymphoma , Lymphoma, B-Cell, Marginal Zone , Lymphoproliferative Disorders , Radiotherapy , Sirolimus , Tacrolimus , Transplant Recipients
18.
Article in English | WPRIM | ID: wpr-739493

ABSTRACT

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving excessive inflammation. Recently, RA associated with a metabolic disorder was revealed to be non-responsive to RA medications. Metformin has been reported to have a therapeutic effect on RA and obesity. The aim of this investigation was to study the therapeutic effect and the underlying mechanism of metformin's action in an experimental model of collagen-induced arthritis (CIA) associated with obesity. Metformin was administered daily for 13 weeks to mice with CIA that had been fed a high-fat diet. Metformin ameliorated the development of CIA in obese mice by reducing autoantibody expression and joint inflammation. Furthermore, metformin decreased the expression levels of pSTAT3 and pmTOR and had a small normalizing effect on the metabolic profile of obese CIA mice. In addition, metformin increased the production of pAMPK and FGF21. Metformin also induced the differentiation of brown adipose tissue (BAT), which led to a reciprocal balance between T helper (Th) 17 and regulatory T (Treg) cells in vitro and in vivo. These results suggest that metformin can dampen the development of CIA in obese mice and reduce metabolic dysfunction by inducing BAT differentiation. Thus, metformin could be a therapeutic candidate for non-responsive RA.


Subject(s)
Adipocytes, Brown , Adipose Tissue, Brown , Animals , Arthritis , Arthritis, Experimental , Arthritis, Rheumatoid , Autoimmune Diseases , Diet, High-Fat , In Vitro Techniques , Inflammation , Joints , Metabolome , Metformin , Mice , Mice, Obese , Models, Theoretical , Obesity
19.
Article in English | WPRIM | ID: wpr-715656

ABSTRACT

BACKGROUND/AIMS: Mind bomb-1 (Mib1) encodes an E3 ubiquitin ligase, which is required for the initiation of Notch signaling. Recently, it was demonstrated that the renal collecting duct plays an important role in renal fibrosis. Here, we investigated the role of Notch signaling in renal fibrosis using conditional knockout mice with the specific ablation of Mib1 in renal collecting duct principal cells. METHODS: Mib1-floxed mice (Mib1f/f ) were crossed with aquaporin 2 (AQP2)-Cre mice in order to generate principal cell-specific Mib1 knockout mice (Mib1f/f :AQP2-Cre+). Unilateral ureteral obstruction (UUO) was performed, and mice were sacrificed 7 days after UUO. RESULTS: After performing the UUO, renal tubulointerstitial fibrosis and the expression of transforming growth factor β were markedly enhanced in the obstructed kidneys of Mib1f/f mice compared with the sham-operated kidney of Mib1f/f mice. These changes were shown to be even more pronounced in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in those of the Mib1f/f mice . Furthermore, the number of TUNNEL-positive cells in renal collecting duct was higher in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in the kidneys of Mib1f/f mice. CONCLUSIONS: Notch signaling in the renal collecting duct plays an important role in the regulation of renal tubulointerstitial fibrosis and apoptosis after UUO.


Subject(s)
Animals , Apoptosis , Aquaporin 2 , Fibrosis , Kidney , Kidney Tubules, Collecting , Mice , Mice, Knockout , Transforming Growth Factors , Ubiquitin-Protein Ligases , Ureter , Ureteral Obstruction
20.
Immune Network ; : e36-2018.
Article in English | WPRIM | ID: wpr-717667

ABSTRACT

Operational tolerance (OT), defined as maintaining stable graft function without immunosuppression after transplant surgery, is an ideal goal for kidney transplant recipients (KTRs). Recent investigations have demonstrated the distinctive features of B cells, T cells, and dendritic cell-related gene signatures and the distributions of circulating lymphocytes in these patients; nonetheless, substantial heterogeneities exist across studies. This study was conducted to determine whether previously reported candidate gene biomarkers and the profiles of lymphocyte subsets of OT could be applied in Korean KTRs. Peripheral blood samples were collected from 153 patients, including 7 operationally tolerant patients. Quantitative real-time PCR and flow cytometry were performed to evaluate gene expression and lymphocyte subsets, respectively. Patients with OT showed significantly higher levels of B cell-related gene signatures (IGKV1D-13 and IGKV4-1), while T cell-related genes (TOAG-1) and dendritic cell-related genes (BNC2, KLF6, and CYP1B1) were not differentially expressed across groups. Lymphocyte subset analyses also revealed a higher proportion of immature B cells in this group. In contrast, the distributions of CD4⁺ T cells, CD8⁺ T cells, mature B cells, and memory B cells showed no differences across diagnostic groups. An OT signature, generated by the integration of IGKV1D-13, IGKV4-1, and immature B cells, effectively discriminated patients with OT from those in other diagnostic groups. Finally, the OT signature was observed among 5.6% of patients who had stable graft function for more than 10 years while on immunosuppression. In conclusion, we validated an association of B cells and their related signature with OT in Korean KTRs.


Subject(s)
B-Lymphocytes , Biomarkers , Flow Cytometry , Gene Expression , Humans , Immunosuppression , Kidney Transplantation , Kidney , Lymphocyte Subsets , Lymphocytes , Memory , Precursor Cells, B-Lymphoid , Real-Time Polymerase Chain Reaction , RNA, Messenger , T-Lymphocytes , Transplant Recipients , Transplants
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