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Melatonin decreases GSDME mediated mesothelial cell pyroptosis and prevents peritoneal fibrosis and ultrafiltration failure

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Science China(Life Sciences) 2024年第2期67卷 360-378页

作者： Hongxia Ruan Xuejuan Li Lina Zhou Zihan Zheng Rulin Hua Xu Wang Yuan Wang Yujie Fan Shuwen Guo Lihua Wang Shafiq ur Rahman Ziwei Wang Yuyuan Wei Shuangyan Yu Rongzhi Zhang Qian Cheng Jie Sheng Xue Li Xiaoyan Liu Ruqiang Yuan Xiaoyan Zhang Lihong Chen Guowang Xu Youfei Guan Jing Nie Hongqiang Qin Feng Zheng Advanced Institute for Medical Sciences Dalian Medical UniversityDalian 116044China Department of Nephrology Second HospitalDalian Medical UniversityDalian 116023China CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Chongqing International Institute for Immunology Chongqing 401320China Department of Nephrology Shenzhen HospitalSouthern Medical UniversityShenzhen 518101China Wuhu Hospital and Health Science Center East China Normal UniversityShanghai 200241China Peking University First Hospital Peking UniversityBeijing 100034China

peritoneal fibrosis together with increased capillaries is the primary cause of peritoneal dialysis *** cell loss is an initiating event for peritoneal *** find that the elevated glucose concentrations in peritoneal dialysate drive mesothelial cell pyroptosis in a manner dependent on caspase-3 and Gasdermin E,driving downstream inflammatory responses,including the activation of ***,pyroptosis is associated with elevated vascular endothelial growth factor A and C,two key factors in vascular angiogenesis and lymphatic vessel *** deficiency mice are protected from high glucose induced peritoneal fibrosis and ultrafiltration *** of melatonin abrogates mesothelial cell pyroptosis through a MT1R-mediated action,and successfully reduces peritoneal fibrosis and angiogenesis in an animal model while preserving dialysis ***,melatonin treatment maintains mitochondrial integrity in mesothelial cells,meanwhile activating m TOR signaling through an increase in the glycolysis product dihydroxyacetone *** effects together with quenching free radicals by melatonin help mesothelial cells maintain a relatively stable internal environment in the face of high-glucose ***,Melatonin treatment holds some promise in preserving mesothelium integrity and in decreasing angiogenesis to protect peritoneum function in patients undergoing peritoneal dialysis.

关键词： melatonin mitochondria pyroptosis GSDME peritoneal fibrosis mTOR

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BMSC-derived Exosomes Ameliorate peritoneal Dialysis-associated peritoneal fibrosis via the Mir-27a-3p/TP53 Pathway

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Current Medical Science 2024年第2期44卷 333-345页

作者： Jun-li ZHAO Lin ZHAO Qiu-nan ZHAN Miao LIU Ting ZHANG Wen-wen CHU Department of Nephrology Shanghai University of Medicine&Health Sciences Affiliated Zhoupu HospitalShanghai 201318China Orthopedic Department Guangming Traditional Chinese Medicine Hospital of Pudong New AreaShanghai 201399China

Objective:peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to ***:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment *** transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of *** and Masson staining were performed to evaluate the extent of *** therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function ***-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%*** were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment *** Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 ***:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to *** RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD *** found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD *** with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious f

关键词： peritoneal fibrosis bone marrow mesenchymal stem cell-derived exosomes miR-27a-3p TP53 epithelialmesenchymal transition

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Strategies for preventing peritoneal fibrosis in peritoneal dialysis patients： new insights based on peritoneal inflammation and angiogenesis

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Frontiers of Medicine 2017年第3期11卷 349-358页

作者： Zhen Zhang Na Jiang Zhaohui Ni Department of Nephrology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 China

peritoneal dialysis （PD） is an established form of renal replacement therapy. Long-term PD leads to morphologic and functional changes to the peritoneal membrane （PM）, which is defined as peritoneal fibrosis, a known cause of loss of peritoneal ultrafiltration capacity. Inflammation and angiogenesis are key events during the pathogenesis of peritoneal fibrosis. This review discusses the pathophysiology of peritoneal fibrosis and recent research progress on key fibrogenic molecular mechanisms in peritoneal inflammation and angiogenesis, including Toll-like receptor ligand-mediated, NOD-like receptor protein 3/interleukin-lp, vascular endothelial growth factor, and angiopoietin-2/Tie2 signaling pathways. Furthermore, novel strategies targeting peritoneal inflammation and angiogenesis to preserve the PM are discussed in depth.

关键词： peritoneal dialysis peritoneal fibrosis inflammation angiogenesis

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Gene delivery in peritoneal dialysis related peritoneal fibrosis research

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Chinese Medical Journal 2012年第12期125卷 2219-2224页

作者： LI Xie-jia SUN Lin XIAO Li LIU Fu-you Department of Nephropathy Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

Objective To summarize the development of gene delivery vectors in peritoneal fibrosis research and discuss the feasibility and superiority of lentiviral vectors. Data sources The data in this article were collected from PubMed database with relevant English articles published from 1995 to 2011. Study selection Articles regarding the gene therapy in peritoneal fibrosis research using non-viral vectors, adenoviral vectors, retroviral vectors, and lentiviral vectors were selected. Data were mainly extracted from 60 articles, which are listed in the reference section of this review. Results Non-viral vector-mediated gene delivery （including naked DNA for ex vivo, oligonucleotides, ultrasound- contrast agent mediated naked gene delivery, etc.） and viral vector-mediated gene delivery （including adenovirus, helper-dependant adenovirus, and retrovirus vectors） have been successfully applied both in the mechanistic investigation and the potential prevention and treatment of peritoneal fibrosis. Conclusions peritoneal fibrosis is a major complication of peritoneal dialysis （PD）. Recently, the wide use of the gene delivery technique made it possible to access and further research peritoneal fibrosis. The use of lentiviral vector is expected to be widely used in PD research in the future due to its advantages in gene delivery.

关键词： peritoneal dialysis peritoneal fibrosis gene delivery non-viral vector viral vector

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The mechanism of Astragalus membranaceus in treating peritoneal fibrosis by intervening the key syndrome and pathology based on Q-marker theory

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Precision Medicine Research 2022年第2期4卷 34-44页

作者： Xin Liu Qian-Cheng Liu Li Liang Guang-Wen Chen Li-Feng Meng Peng Zeng Guangxi University of Traditional Chinese Medicine Nanning 530001China The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine Nanning 530023China Tongji Medical College Huazhong University of Science and TechnologyWuhan 430030China

Objective:To evaluate the mechanism of Astragalus membranaceus(AM)by intervening peritoneal mesothelial cells(PMCs),epithelial-mesenchymal transition(EMT),and spleen deficiency syndrome(SDS)in peritoneal fibrosis(PF),we base on employing the strategy of Q-marker theory combination network pharmacology ***:First,we obtained the Q-markers of AM by searching the relevant literature and its pharmacological information was collected based on *** SwissTargetPrediction and pharmmaper were employed to predict its potential ***,GeneCards,DisGeNET,and OMIM databases were employed to search the related targets of EMT,SDS,and ***2.1 tool was employed to obtain the intersection targets of AM and the three;then the“AM potential target-SDS-EMT-PF”Venn diagram was *** common targets of AM,EMT and SDS were uploaded to the STRING database and obtained the PPI protein interaction network *** 3.7.2 was employed to evaluate the core target of PPI *** and Metascape databases were used to analyze protein type,GO biological process,and KEGG ***,a network diagram of the“TCM-component-disease target-pathway”was ***:A total of 10 AM Q-makers were screened out,corresponding to 335 targets of AM,2,728 targets of SDS,373 of EMT,and 612 PF targets were *** them,there are 155 common AM targets related to SDS and *** targets such as ALB,AKT1,VEGFA,TNF,EGFR,CASP3,SRC,STAT3,HSP90AA1,and ESR1 were *** core drug include quercetin,astragalosideIII,Calycosin-7-O-beta-D-glucoside,astragalosideIV,*** types of PPI proteins include protein modification enzymes,metabolite transferases,transmembrane signal receptors,*** processes include the regulation of kinase activity,the positive regulation of transferase activity,and the regulation of kinase *** key pathways may include PI3K-Akt signaling pathways,the non-smad pathway of the TGF-βsignaling pathway,and the AGE-RAGE signa

关键词： Astragalus membranaceus network pharmacology peritoneal fibrosis epithelial-mesenchymal transition Spleen deficiency syndrome PI3K-Akt signing pathway

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Abdominal cocoon syndrome-a rare culprit behind small bowel ischemia and obstruction:Three case reports

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 955-965页

作者： Witcha Vipudhamorn Tawan Juthasilaparut Pawit Sutharat Suwan Sanmee Ekkarin Supatrakul Department of Colorectal Surgery Chiang Mai UniversityChiang Mai 50200Thailand Department of Surgery Lampang HospitalLampang 52000Thailand

BACKGROUND Abdominal cocoon syndrome(ACS)represents a category within sclerosing encapsulating peritonitis,characterized by the encapsulation of internal organs with a fibrous,cocoon-like membrane of unknown origin,resulting in bowel obstruction and *** this condition before surgery poses a cha-llenge,often requiring confirmation during *** this context,we depict three instances of ACS:One linked to intestinal obstruction,the second exclu-sively manifesting as intestinal ischemia without any obstruction,and the final case involving a discrepancy between the radiologist and the *** SUMMARY Three male patients,aged 53,58,and 61 originating from Northern Thailand,arrived at our medical facility complaining of abdominal pain without any prior *** vital signs remained stable during the *** diagnosis of abdominal cocoon was confirmed through abdominal computed tomography(CT)before *** the first case,the CT scan revealed capsules around the small bowel loops,showing no enhancement,along with mesenteric congestion affecting both small and large bowel loops,without a clear *** second case showed intestinal obstruction due to an encapsulated capsule on the CT *** the final case,a patient presented with recurring abdominal ***,the radiologist suspected enteritis as the cause after the CT ***,a detailed review led the surgeon to suspect encapsulating peritoneal sclerosis(ACS)and subsequently perform *** surgical procedure involved complete removal of the encapsulating structure,resection of a portion of the small bowel,and end-to-end *** complications occurred during surgery,and the patients had a smooth recovery after surgery,eventually discharged in good *** histopathological examination of the fibrous membrane(cocoon)across all cases consistently revealed the presence of fibro-collagenous tissue,without any indications of *** Indivi

关键词： Sclerosing encapsulation peritonitis Abdominal cocoon peritoneal fibrosis peritoneal encapsulation syndrome Intestinal obstruction Surgery Case report

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Targeting cannabinoid signaling for peritoneal dialysisinduced oxidative stress and fibrosis

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World Journal of Nephrology 2017年第3期6卷 111-118页

作者： Chih-Yu Yang Yat-Pang Chau Ann Chen Oscar Kuang-Sheng Lee Der-Cherng Tarng An-Hang Yang Division of Nephrology Department of MedicineTaipei Veterans General Hospital School of Medicine National Yang-Ming University Institute of Clinical Medicine National YangMing University Faculty of Medicine Mackay Medical College Department of Pathology Tri-Service General HospitalNational Defense Medical Center Department of Orthopedic Surgery Taipei City Hospital Stem Cell Research Center National Yang-Ming University Department of Medical Research and Department of Orthopedic Surgery Taipei Veterans General Hospital Department of Pathology Taipei Veterans General Hospital

Long-term exposure to bioincompatible peritoneal dialysis(PD) solutions frequently results in peritoneal fibrosis and ultrafiltration failure,which limits the life-long use of and leads to the cessation of PD ***,it is important to elucidate the pathogenesis of peritoneal fibrosis in order to design therapeutic strategies to prevent its *** fibrosis is associated with a chronic inflammatory status as well as an elevated oxidative stress(OS) *** uremia per se,OS also results from chronic exposure to high glucose load,glucose degradation products,advanced glycation end products,and hypertonic *** targeting the cannabinoid(CB) signaling pathway has been reported in several chronic inflammatory diseases with elevated *** recently reported that the intra-peritoneal administration of CB receptor ligands,including CB_1 receptor antagonistsand CB_2 receptor agonists,ameliorated dialysis-related peritoneal *** targeting the CB signaling pathway has been reported to be beneficial in attenuating the processes of several chronic inflammatory diseases,we reviewed the interaction among the cannabinoid system,inflammation,and OS,through which clinicians ultimately aim to prolong the peritoneal survival of PD patients.

关键词： Reactive oxygen species peritoneal fibrosis peritoneal dialysis Cannabinoid signaling Oxidative stress

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Blocking Posttranslational Core Fucosylation Ameliorates Rat peritoneal Mesothelial Cell Epithelial-Mesenchymal Transition

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Chinese Medical Journal 2017年第18期130卷 2147-2155页

作者： Long-Kai Li Nan Wang Wei-Dong Wang Xiang-Ning Du Xin-Yu Wen Ling-Yu Wang Yi-Yao Deng Da-Peng Wang Hong-Li Lin Graduate School Dalian Medical University Dalian Liaoning 116044 China Department of Nephrology Liaoning Translational Medicine Center of Nephrology The First Affiliated Hospital of Dalian Medical University DalianLiaoning 116011 China

Background：Core fucosylation （CF）,catalyzed by α-1,6 fucosyltransferase （Fut8） in mammals,plays an important role in pathological processes through posttranslational modification of key signaling receptor proteins,including transforming growth factor （TGF）-β receptors and platelet-derived growth factor （PDGF） ***,its effect on peritoneal fibrosis is ***,we investigated its influence on epithelial-mesenchymal transition （EMT） of rat peritoneal mesothelial cells （PMCs） in vitro induced by a high-glucose （HG） culture ***：Rat PMCs were first cultured in a HG （2.5%） culture solution to observe the CF expression level （fluorescein isothiocyanate-lens culinaris agglutinin）,we next established a knockdown model of rat PMCs in vitro with Fut8 small interfering RNA （siRNA） to observe whether inhibiting CF decreases the messenger RNA （mRNA） expression and protein expression of Fut8 and reverses EMT *** PMCs were randomly divided into control group,mock group （transfected with scrambled siRNA）,Fut8 siRNA group,HG group,HG ＋ mock group,and HG ＋ Fut8 siRNA ***,we examined the activation of TGF-β/Smad2/3 signaling and PDGF/extracellular signal-regulated kinase （ERK） signaling to observe the influence of CF on ***：CF,Fut8 mRNA,and protein expression were all significantly upregulated in HG-induced EMT model than those in the control rat PMCs （P 〈 0.05）.Fut8 siRNA successfully blocked CF of TGF-β receptors and PDGF receptors and attenuated the EMT status （E-cadherin and α-SMA and phenotypic changes） in HG-induced rat *** TGF-β/Smad2/3 signaling,Fut8 siRNA did not suppress the protein expression of TGF-3 receptors and Smad2/3;however,it significantly suppressed the phosphowlation of Smad2/3 （relative expression folds of HG ＋ Fut8 group *** group：7.6 ± 0.4 vs.15.1 ± 0.6,respectively,P 〈 0.05）.In PDGF/ERK signaling,Fut8 siRNA did not suppress the protein expression of PDGF receptors and ERK,but it significantly suppres

关键词： α-1,6 Fucosyltransferase: Core Fucosylation: Epithelial Mesenchymal Transition peritoneal fibrosis

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