Yanna Dou

IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal mesothelial cells possibly through the JAK2/STAT3 signaling pathway

Long-term peritoneal dialysis (PD) therapy results in functional and structural alteration of the peritoneal membrane, including epithelial-to-mesenchymal transition (EMT). Interleukin 6 (IL-6) is a local pleiotropic cytokine, hypothesized to play an important role in EMT. This study was designed to investigate the role of IL-6 in EMT and peritoneal membrane dysfunction in long-term PD patients by assessing the level of IL-6 in dialysate and exploring the relationship between IL-6, the related signaling pathway JAK2/STAT3, and EMT, using in vitro cellular and molecular techniques. Plasma and dialysate levels of IL-6 were significantly higher in PD ultrafiltration failure patients compared with patients without ultrafiltration failure and were negatively correlated with measures of PD adequacy. In vitro IL-6 treatment changed human peritoneal mesothelial cell phenotype from a typical cobblestone-like to a fibroblast-like appearance and increased cell viability. IL-6 treatment increased α-smooth muscle actin and vascular endothelial growth factor expression but decreased E-cadherin expression. IL-6 treatment activated the JAK/STAT signaling pathway. However, the JAK2/STAT3 inhibitor WP1066 prevented IL-6-induced activation of the JAK2/STAT3 pathway and EMT. We conclude that IL-6 promotes the EMT process, possibly by activating the JAK2/STAT3 signaling pathway. IL-6 may serve as a novel therapeutic target for preventing EMT, and preservation of the peritoneal membrane may arise from these studies.

The Geriatric Nutritional Risk Index May Predict Healthcare Costs and Health Transitions during Hemodialysis in China

BACKGROUND AND OBJECTIVES The aim of the present study was to retrospectively analyze the relationship between the Geriatric Nutritional Risk Index (GNRI) at baseline and healthcare costs of three-month as well as the risk of quality-of-life score at the 6-month follow-up for Chinese hemodialysis patients. METHODS AND STUDY DESIGN One hundred patients who had been on maintenance hemodialysis were enrolled in this study. The general characteristics, laboratory test results and GNRI of the patients at baseline were recorded. The healthcare costs and quality-of-life scores were determined at the follow-up examination. RESULTS Patients were divided into two groups according to their median GNRI at baseline: a lower GNRI group (GNRI <86.4) and a higher GNRI group (GNRI >86.4). The patients in the lower GNRI group exhibited reduced hemoglobin (74.7±13.1 g/dL vs 82.3±15.2 g/dL, p<0.05) and albumin (27.4±3.3 g/L vs 34.5±4.0 g/L, p<0.05) as well as reduced body weight (62.7±9.5 kg vs 68.0±9.2 kg, p<0.05) at baseline. The medication cost at follow-up was higher in the lower GNRI group (RMB 3,238±1,534 vs RMB 2,378±1,048, p<0.05). And a lower GNRI at baseline was associated with increased future medication costs and worse health in hemodialysis patients. CONCLUSIONS The present study suggests that a lower GNRI in hemodialysis patients may be associated with an increased risk of higher future healthcare costs as well as worse health.

Inhibition of microRNA-182-5p contributes to attenuation of lupus nephritis via Foxo1 signaling

&NA; MiR‐182–5p suppresses expression of Foxo1 that is a protective factor in renal disorders and is up‐regulated in systemic lupus erythematosus patients. Thus, we hypothesized that dys‐function of miR‐182–5p/Foxo1 axis contributed to development of lupus nephritis (LN). Firstly, we investigated the expressions of miR‐182–5p and Foxo1 in LN patients and during growth of LN MRL/lpr mice. Then we subjected MRL/lpr mice to the injection of miR‐182–5p antagomirs and assessed the effect of miR‐182–5p inhibition on renal structure and function. In vitro, we administrated renal cell lines with TGF‐&bgr;1 to explore the relation between renal fibrosis and miR‐182–5p. The level of miR‐182–5p was up‐regulated in high Chronicity Index patients while the level of Foxo1 was suppressed. The progression of LN in mice was associated with the increased level of miR‐182–5p and the decreased level of Foxo1. The inhibition of miR‐182–5p ameliorated renal structure and function impairments associated with LN, along with the increased expression of Foxo1. The administration of TGF‐&bgr;1 in vitro increased the expression of miR‐182–5p in renal cells in an overall dose‐dependent manner. The current study demonstrated that the expression of miR‐182–5p was increased in LN patients, contributing to the suppression of Foxo1 and development of LN. HighlightsMiR‐182–5p is up‐regulated in LN patients.Foxo1 is down‐regulated in LN patients.MiR‐185–5p promotes development of LN by inhibiting Foxo1.Inhibition of miR‐182–5p attenuates LN symptoms.

Human anti-thrombospondin type 1 domain-containing 7A antibodies induce membranous nephropathy through activation of lectin complement pathway

To investigate whether the human anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibody-induced membranous nephropathy (MN) is mediated by activating lectin complement pathway. Automatic biochemical apparatus was used to assess renal function of mice. The serum levels of anti-THSD7A antibodies and complement were tested by using ELISA. The expression level of THSD7A and mannose-binding lectin (MBL) in clinical tissue, and the histological features of MN in mice were examined by immunochemical methods. We found that THSD7A, MBL, and complement expression level from patients with circulating anti-THSD7A antibodies were significantly higher than that in normal group. Furthermore, difference of renal function in anti-THSD7A antibody-containing serum treatment groups and control groups was significant. Meanwhile, human anti-THSD7A autoantibodies activated the complement system and induced the histological features of MN in mice. In conclusion, human anti-THSD7A antibodies induce MN through activating MBL lectin complement pathway in mice.

The protective effect of mycophenolate mofetil on residual renal function in peritoneal dialysis patients: an open label feasibility study.

This study aims to evaluate the safety of mycophenolate mofetil (MMF) and its effect on residual renal function (RRF) during peritoneal dialysis (PD).

Independent Association between Hyperuricemia and Histopathological Parameters in Chinese Patients with Henöch-Schönlein Purpura Nephritis

BACKGROUND This study aimed to investigate the role of hyperuricemia in the development of histopathological changes in HSPN. METHODS Clinical and laboratory data pertaining to 139 adult HSPN patients with and without elevated serum uric acid levels were retrospectively evaluated. There was a 14.4% prevalence of hyperuricemia in patients with HSPN. RESULTS Patients with hyperuricemia had higher levels of cystatin C and urine β2-microglobulin and lower levels of HDL-C in comparison to that in patients with normal serum uric acid levels (p < 0.05). Patients with hyperuricemia had higher scores of interstitial inflammation, tubular atrophy, interstitial fibrosis, glomerulosclerosis as compared to those normouricemic patients (p < 0.05). Serum uric acid was found to be correlated independently with the presence of interstitial inflammation, tubular atrophy, interstitial fibrosis, and glomerulosclerosis by multivariate analysis (p < 0.05). CONCLUSIONS High serum uric acid may be independently correlated with the development of tubulointerstitial lesions as well as glomerulosclerosis in HSPN.