Shanghai Key Laboratory of Organ Transplantation

Shanghai, China

Shanghai Key Laboratory of Organ Transplantation

Shanghai, China
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Chen S.,Fudan University | Yang C.,Fudan University | Yang C.,Shanghai Key Laboratory of Organ Transplantation | Zhu L.,Fudan University | Jiang J.,Fudan University
International Journal of Clinical and Experimental Medicine | Year: 2017

Proteomics provides abundant information on the relationships between biological molecules and disease mechanisms. We selected 507 signaling proteins in the bloodstream using antibody microarray technology to identify the difference in protein expression between acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients and healthy subjects. Biological analysis of the 507 proteins revealed systemic dysregulation of inflammation, immune responses and apoptosis in ARDS. Protein-protein networks that were involved in ALI/ARDS are described. The most important signaling pathways related to ALI/ARDS are cytokine-cytokine receptor interactions and chemokine signaling pathways. IL-23, glypican 3, and leptin R (receptor) might be potential predictors for ALI/ ARDS. This study identified novel potential biomarkers that might be involved in the inflammatory response, immune responses, and metabolism in ALI and ARDS. © 2017, E-Century Publishing Corporation. All rights reserved.

Qi G.,Shanghai Key Laboratory of Organ Transplantation | Lin M.,Shanghai Key Laboratory of Organ Transplantation | Xu M.,Shanghai Key Laboratory of Organ Transplantation | Manole C.G.,University of Bucharest | And 2 more authors.
Journal of Cellular and Molecular Medicine | Year: 2012

Renal interstitial cells play an important role in the physiology and pathology of the kidneys. As a novel type of interstitial cell, telocytes (TCs) have been described in various tissues and organs, including the heart, lung, skeletal muscle, urinary tract, etc. ( However, it is not known if TCs are present in the kidney interstitium. We demonstrated the presence of TCs in human kidney cortex interstitium using primary cell culture, transmission electron microscopy (TEM) and in situ immunohistochemistry (IHC). Renal TCs were positive for CD34, CD117 and vimentin. They were localized in the kidney cortex interstitial compartment, partially covering the tubules and vascular walls. Morphologically, renal TCs resemble TCs described in other organs, with very long telopodes (Tps) composed of thin segments (podomers) and dilated segments (podoms). However, their possible roles (beyond intercellular signalling) as well as their specific phenotype in the kidney remain to be established. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Lin M.,Sun Yat Sen University | Li L.,Shanghai Key Laboratory of Organ Transplantation | Pokhrel G.,Sun Yat Sen University | Qi G.,Sun Yat Sen University | And 2 more authors.
BMC Complementary and Alternative Medicine | Year: 2014

Background: Renal ischemia-reperfusion injury (IRI) increases the rates of acute kidney failure, delayed graft function, and early mortality after kidney transplantation. The pathophysiology involved includes oxidative stress, mitochondrial dysfunction, and immune-mediated injury. The anti-oxidation, anti-apoptosis, and anti-inflammation properties of baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, have been verified. This study therefore assessed the effects of baicalin against renal IRI in rats. Methods: Baicalin was intraperitoneally injected 30 min before renal ischemia. Serum and kidneys were harvested 24 h after reperfusion. Renal function and histological changes were assessed. Markers of oxidative stress, the Toll-like receptor (TLR)2 and TLR4 signaling pathway, mitochondrial stress, and cell apoptosis were also evaluated. Results: Baicalin treatment decreased oxidative stress and histological injury, and improved kidney function, as well as inhibiting proinflammatory responses and tubular apoptosis. Baicalin pretreatment also reduced the expression of TLR2, TLR4, MyD88, p-NF-κB, and p-IκB proteins, as well as decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. Conclusions: Baicalin may attenuate renal ischemia-reperfusion injury by inhibiting proinflammatory responses and mitochondria-mediated apoptosis. These effects are associated with the TLR2/4 signaling pathway and mitochondrial stress. © 2014 Lin et al.; licensee BioMed Central Ltd.

Li L.,Sun Yat Sen University | Li L.,Shanghai Key Laboratory of Organ Transplantation | Lin M.,Sun Yat Sen University | Lin M.,Shanghai Key Laboratory of Organ Transplantation | And 12 more authors.
Journal of Cellular and Molecular Medicine | Year: 2014

Telocytes (TCs), a distinct type of interstitial cells, have been identified in many organs via electron microscopy. However, their precise function in organ regeneration remains unknown. This study investigated the paracrine effect of renal TCs on renal tubular epithelial cells (TECs) in vitro, the regenerative function of renal TCs in renal tubules after ischaemia-reperfusion injury (IRI) in vivo and the possible mechanisms involved. In a renal IRI model, transplantation of renal TCs was found to decrease serum creatinine and blood urea nitrogen (BUN) levels, while renal fibroblasts exerted no such effect. The results of histological injury assessments and the expression levels of cleaved caspase-3 were consistent with a change in kidney function. Our data suggest that the protective effect of TCs against IRI occurs via inflammation-independent mechanisms in vivo. Furthermore, we found that renal TCs could not directly promote the proliferation and anti-apoptosis properties of TECs in vitro. TCs did not display any advantage in paracrine growth factor secretion in vitro compared with renal fibroblasts. These data indicate that renal TCs protect against renal IRI via an inflammation-independent pathway and that growth factors play a significant role in this mechanism. Renal TCs may protect TECs in certain microenvironments while interacting with other cells. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Liu J.-Y.,Fudan University | Ding J.,Fudan University | Lin D.,Fudan University | He Y.-F.,Fudan University | And 8 more authors.
Journal of Magnetic Resonance Imaging | Year: 2013

Purpose: To evaluate regional brain iron deposition in minimal hepatic encephalopathy (MHE) patients using T2*-weighted gradient-echo imaging and to explore the relationship between T2* MR changes and cognitive performance. Materials and Methods: Forty hepatitis-B virus (HBV)-related cirrhotic patients and 22 age-, sex-, and education-matched healthy controls were included in this study. Of the patients, twenty eight patients were diagnosed with MHE. All subjects were administered Number Connection Test-A (NCT-A), Letter Digit Substitution Test (LDST), Rey-Osterrieth Complex Figure Test (RCFT), and the Mini-Mental State Examination (MMSE). T2*-weighted gradient-echo images were acquired using 3 Tesla MRI. Phase values (putative iron levels) in the frontal-basal ganglia-thalamocortical circuits were measured. Spearman correlation and multiple linear regression analysis were performed. Results: MHE patients exhibited significantly prolonged NCT-A time and decreased LDST, RCFT immediate and delayed recall scores. Significant decreases of phase values in the bilateral putamen were detected in MHE patients compared to without MHE patients and controls. Multiple linear regression analysis confirmed significant correlations between the phase values in the putamen and right frontal white matter and cognitive performances by MHE patients. Conclusion: Decreased phase values in the frontal cortical-basal ganglial circuits independently contribute to cognitive impairments in MHE patients. J. Magn. Reson. Imaging 2013;37:179-186. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Hu L.,Fudan University | Yang C.,Fudan University | Yang C.,Shanghai Key Laboratory of Organ Transplantation | Zhao T.,Shanghai Key Laboratory of Organ Transplantation | And 7 more authors.
Journal of Surgical Research | Year: 2012

Background: Tubulointerstitial inflammation is the characteristics of renal ischemia reperfusion injury (IRI) that is inevitable in kidney transplantation. Erythropoietin (EPO) has recently been shown to have protective effects on renal IRI by anti-apoptosis and anti-oxidation. Here, the effect and mechanism of EPO on renal IRI were further investigated, with a focus on tubulointerstitial inflammation. Materials and Methods: Male Sprague-Dawley rats were administrated with saline or EPO prior to IRI induced by bilateral renal pedicle clamping. Twenty-four hours following reperfusion, the effects of EPO on renal IRI were assessed by renal function and structure, tubulointerstitial myeloperoxidase (MPO) positive neutrophils, and proinflammatory mediator gene expression. The translocation and activity of NF-κB in renal tissues were also evaluated. Results: Compared with control groups, the EPO treated group exhibited lower serum urea and creatinine levels, limited tubular necrosis with a lower score of renal histological lesion. MPO positive cells in the tubulointerstitial area were greatly increased by IRI, but significantly reduced by the treatment of EPO. The gene expression of proinflammatory cytokines (IL-1β, IL-6, IL-10, and TNF-α) and chemokine (MCP-1) was also significantly decreased by EPO. In addition, less activation and nuclear-translocation of NF-κB was observed in the kidney treated by EPO as well. Conclusion: EPO improved renal function and structure in IRI rats via reducing neutrophils in the tubulointerstitium, the production of proinflammatory cytokines and chemokine, as well as the activation and nuclear-translocation of NF-κB. EPO may have potential clinical applications as an anti-inflammation agent clinically for a wide range of injury. © 2012 Elsevier Inc. All rights reserved.

He W.-Y.,Fudan University | He W.-Y.,Shanghai Institute of Imaging Medicine | Jin Y.-J.,Fudan University | Jin Y.-J.,Shanghai Institute of Imaging Medicine | And 5 more authors.
Ultrasound in Medicine and Biology | Year: 2014

Acoustic radiation force impulse (ARFI) quantification, a novel ultrasound-based elastography method, has been used to measure liver fibrosis. However, few studies have been performed on the use of ARFI quantification in kidney examinations. We evaluated renal allograft stiffness using ARFI quantification in patients with stable renal function (n=52) and those with biopsy-proven allograft dysfunction (n=50). ARFI quantification, given as shear wave velocity (SWV), was performed. The resistance index (RI) was calculated by pulsed-wave Doppler ultrasound, and clinical and laboratory data were collected. Morphologic changes in transplanted kidneys were diagnosed by an independent pathologist. Mean SWV was more significantly negatively correlated with estimated glomerular filtration rate (eGFR) (r=-0.657, p<0.0001) than was RI (r=-0.429, p=0.0004) in transplanted kidneys. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of quantitative ultrasound in the diagnosis of renal allograft dysfunction were 72.0% and 86.5% (cutoff value=2.625), respectively. The latter values were better than those of RI, which were 62.0% and 69.2% (cutoff value=0.625), respectively. The coefficient of variation for repeat SWV measurements of the middle part of transplanted kidney was 8.64%, and inter-observer agreement on SWV was good (Bland-Altman method, ICC=0.890). In conclusion, tissue elasticity quantification by ARFI is more accurate than the RI in diagnosing renal allograft function. © 2014 World Federation for Ultrasound in Medicine & Biology.

Li Q.-L.,Fudan University | Gu F.-M.,Fudan University | Wang Z.,Fudan University | Jiang J.-H.,Fudan University | And 10 more authors.
PLoS ONE | Year: 2012

Background: Rapamycin is an attractive approach for the treatment and prevention of HCC recurrence after liver transplantation. However, the objective response rates of rapamycin achieved with single-agent therapy were modest, supporting that rapamycin resistance is a frequently observed characteristic of many cancers. Some studies have been devoted to understanding the mechanisms of rapamycin resistance, however, the mechanisms are cell-type-dependent and studies on rapamycin resistance in HCC are extremely limited. Methodology/Principal Findings: The anti-tumor sensitivity of rapamycin was modest in vitro and in vivo. In both human and rat HCC cells, rapamycin up-regulated the expression and phosphorylation of PDGFRβ in a time and dose-dependent manner as assessed by RT-PCR and western blot analysis. Using siRNA mediated knockdown of PDGFRβ, we confirmed that subsequent activation of AKT and ERK was PDGFRβ-dependent and compromised the anti-tumor activity of rapamycin. Then, blockade of this PDGFRβ-dependent feedback loop by sorafenib enhanced the anti-tumor sensitivity of rapamycin in vitro and in an immunocompetent orthotopic rat model of HCC. Conclusions: Activation of PI3K/AKT and MAPK pathway through a PDGFRβ-dependent feedback loop compromises the anti-tumor activity of rapamycin in HCC, and blockade of this feedback loop by sorafenib is an attractive approach to improve the anti-tumor effect of rapamycin, particularly in preventing or treating HCC recurrence after liver transplantation. © 2012 Li et al.

PubMed | Fudan University and Shanghai Key Laboratory of Organ Transplantation
Type: Journal Article | Journal: BMC immunology | Year: 2016

Although histone methyltransferases EZH2 has been proved to have significant regulatory effect on the immune rejection after hematopoietic stem cell transplantation, its role in solid-organ transplantation remains uncovered. In this study, we investigate whether histone methylation regulation can impact renal allograft rejection in rat models.Allogeneic rat renal transplantation model (Wistar to Lewis) was established, and the recipients were administrated with EZH2 inhibitor DZNep after transplantation. Renal allografts and peripheral blood were collected on day 5 after transplantation for histological examination and mechanism investigation. We found that inhibition of EZH2 by DZNep after transplantation significantly ameliorated acute rejection (AR), with decreased histological injury and reduced inflammatory infiltration in renal allografts. Attenuation of AR was due to the prohibited activation of alloreactive T cells, the subsequent impaired production of inflammatory cytokines, and also the elevated apoptosis of alloreactive T cells in both renal allografts and periphery. However, inhibition of EZH2 did not increase the regulatory T cells during the AR.Disruption of EZH2 by DZNep suppressed the immune responses of alloreactive T cells and ameliorated AR of renal allografts. This suggests a therapeutic potential of targeting histone methyltransferases EZH2 in treating allograft rejection after solid organ transplantation.

PubMed | Fudan University, Shanghai Key Laboratory of Organ Transplantation and Soochow University of China
Type: | Journal: Cell death & disease | Year: 2016

Acute kidney injury (AKI) is a common and severe clinical condition with a heavy healthy burden around the world. In spite of supportive therapies, the mortality associated with AKI remains high. Our limited understanding of the complex cell death mechanism in the process of AKI impedes the development of desirable therapeutics. Necroptosis is a recently identified novel form of cell death contributing to numerable diseases and tissue damages. Increasing evidence has suggested that necroptosis has an important role in the pathogenesis of various types of AKI. Therefore, we present here the signaling pathways and main regulators of necroptosis that are potential candidate for therapeutic strategies. Moreover, we emphasize on the potential role and corresponding mechanisms of necroptosis in AKI based on recent advances, and also discuss the possible therapeutic regimens based on manipulating necroptosis. Taken together, the progress in this field sheds new light into the prevention and management of AKI in clinical practice.

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