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Multinucleated giant cells of bladder mucosa are modified telocytes:Diagnostic and immunohistochemistry algorithm and relation to PDL1 expression score

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世界临床病例杂志 2023年第26期11卷 6091-6104页

作者： Milena Gulinac Tsvetelina Velikova Dorian Dikov General and Clinical Pathology Medical University of PlovdivPlovdiv 4002Bulgaria Medical Faculty Sofia UniversitySt.Kliment OhridskiSofia 1407Bulgaria Pathology Grand Hospital de l’Este FrancilienJossigny 1000France

BACKGROUND Multinucleated giant cells(MGCs)in bladder carcinomas are poorly studied.AIM To describe the function,morphogenesis,and origin of mononuclear and MGCs in urothelial carcinoma(UC)of the bladder in Bulgarian and French patients.METHODS Urothelial bladder carcinomas(n=104)from 2016-2020 were analyzed retrospectively using immunohistochemical(IHC)and histochemical stain examination.Giant cells in the bladder stroma were found in 35.6%of cases,more often in highgrades.RESULTS We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers(vimentin,smooth muscle actin,desmin,and CD34)and the macrophage marker CD68.Furthermore,IHC studies revealed the following profile of these cells:Positive for p16;negative for epithelial(CK AE1/AE3 and GATA-3),vascular(CD31),neural(PS100 and CKIT),cambial,blastic(CD34-blasts and C-KIT),and immune markers(IG G,immunoglobulin G4,and PD-L1);no proliferative activity,possess no specific immune function,and cannot be used to calculate the Combined Positive Score scale.CONCLUSION In conclusion,the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant,although nonspecific,histological marker for chronic bladder damage,reflecting the chronic irritation or inflammation.Likewise,according to the morphological and IHC of the mono-and multinucleated giant cells in the bladder,they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.

关键词： Multinucleated giant cells Telocytes Urothelial bladder carcinoma Immunohistochemical Vimentin Smooth muscle actin desmin CD34 CD68 p16 Algorithm PD-L1 Chronic inflammation

Time course of expression of intermediate filament protein vimentin,nestin and desmin in rat renal glomerular injury

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Chinese Medical Journal 2007年第13期120卷 1203-1205页

作者： ZOU Jun CHANG Tian-hui CHANG He Eishin Yaoita Yutaka Yoshida Masaaki Nameta Tadashi Yamamoto JIN Xin Department of Pharmacy School of Medical Sciences Xiamen University Xiamen 361005 China Department of Clinical Pharmacology School of Pharmaceutical Sciences China Medical University Shengyang 110001 China Division of Cardiology Niigata University Graduate School of Medical and Dental Sciences 1-757 Asahimachi-dori Niigata 951-8510 Japan Department of Structural Pathology Institute of NephrologyNiigata University Graduate School of Medical and Dental Sciences 1-757 Asahimachi-dori Niigata 951-8510 Japan

Podocytes in renal glomemlus express unusual intermediate filament proteins （IFs） for visceral epithelial cells. IFs cytoskeleton is mainly composed of vimentin, nestin and desmin. Tissue injury is often accompanied by changes in gene expression of IFs. Enhanced desmin staining in variety of rat experimental including 2 4 puromycin nephrosis. It has not podocytes are observed in a models of podocyte injury aminonucleoside （PAN） been elucidated whether expression of vimentin and nestin is up-regulated in podocyte injury. To further gain insight into expression of IFs in podocytes, we investigated the time course of vimentin, nestin and desmin in PAN nephrosis.

关键词： intermediate filament vimentin nestin desmin kidney

Effect of dl-praeruptorin A on desmin and vimentin content in rat ischemia/reperfusion myocardiocytes

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Chinese Medical Journal 2007年第24期120卷 2256-2259页

作者： CHANG He CHU Xiao-yu ZOU Jun CHANG Tian-hui Division of Cardiology Graduate School of Medical and DentalSciences Niigata University 1-757 Asahimachi-dori Niigata951-8510 Japan Department of Clinical Pharmacology School of PharmaceuticalSciences China Medical University Shengyang 110001 China Department of Pharmacy School of Medical Sciences Xiamen University Xiamen 361005 China

Background Intermediate filament （IF） proteins have been thought to play a role in nuclear centration, organelle movement and maintenance of cell shape, dl-praeruptorin A （Pd-la）, a novel Ca^2＋-influx blocker and K^＋-channel opener isolated from Chinese traditional herbal medicine Qian-Hu, has been demonstrated to inhibit expression of apoptosis related proteins and reduce the level of proinflammatory factors in ischemia/reperfusion myocardiocytes. Morphologically, whether Pd-la effects myocardiocyte IFs remains unclear. The purpose of this study was, for the first time, to evaluate the in vivo effects of Pd-la on IF desmin and vimentin content in order to further explore its cardioprotection against ischemia and elucidate its mechanism of action. Methods Rats underwent a 30 minutes coronary occlusion followed by 120 minutes reperfusion. Assessment of desmin and vimentin content of myocardiocytes was performed by immunohistochemistry, Western blot, Hematoxylin-Eosin staining and densitometry. Results Pretreatment with i.v. infusion of Pd-la prior to ischemia significantly increased desmin and vimentin content and alleviated defects caused by the ischemia/reperfusion insult, e.g. with Pd-la at a dose of 0.5 or 1.0 mg/kg, integrated density values of desmin were increased from 61 478 ± 10 074 to 177 408 ±10 395 and 195 784±20 057, and vimentin from 59 189± 19 853 to 164 781± 19 543 and 185 696± 20 957 （P〈0.01, vs placebo）, respectively. The recovery of desmin seemed to be stronger and appeared earlier than that of vimentin. Conclusion Pd-la protectively increased IF desmin and vimentin content in ischemia/reperfusion myocardiocytes, which might be partially responsible for its cardioprotection against ischemia.

关键词： dl-praeruptorin A desmin vimentin intermediate filament ischemia myocardiocyte

活性维生素D_(3)对阿霉素肾病模型大鼠足细胞及特异性损伤因子desmin的影响

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中国老年学杂志 2022年第2期42卷 416-420页

作者：马国英赵丹陈亚茹刘馨馨罗星石河子大学医学院生化教研室新疆石河子832002 石河子大学医学院第一附属医院肾病科新疆石河子832002

目的研究活性维生素D_(3)〔1,25-(OH)_(2)D_(3)〕对阿霉素肾脏病模型大鼠足细胞损伤因子desmin表达的影响。方法90只SD大鼠被随机分为对照组、模型组、治疗组,每组各30只,对模型组和治疗组使用一次性尾静脉注射阿霉素建模。每天对治疗... 详细信息

目的研究活性维生素D_(3)〔1,25-(OH)_(2)D_(3)〕对阿霉素肾脏病模型大鼠足细胞损伤因子desmin表达的影响。方法90只SD大鼠被随机分为对照组、模型组、治疗组,每组各30只,对模型组和治疗组使用一次性尾静脉注射阿霉素建模。每天对治疗组给予1,25-(OH)_(2)D_(3)灌胃治疗,对照组与模型组给予等量的花生油灌胃。造模后第2周末收集24 h尿、腹主动脉采血测量尿蛋白与血生化指标,鉴定模型是否建造成功;取肾组织进行后续的组织学观察和分子水平检测,苏木素-伊红(HE)染色、Masson染色用于肾小球病理损伤观察;使用免疫组织化学、免疫荧光、Western印迹分析检测足细胞损伤因子desmin的表达变化。结果与对照组相比,模型组和治疗组24 h尿蛋白(UTP)、尿素氮(BUN)、血肌酐(Cr)、总胆固醇(TC)水平均显著升高,而总蛋白(TP)、白蛋白(Alb)水平均显著下降(均Pdesmin蛋白表达随着损伤时间的增加而升高,使用1,25-(OH)_(2)D_(3)治疗后,desmin显著下降。结论1,25-(OH)_(2)D_(3)可降低足细胞损伤因子desmin的表达、改善足细胞的损伤,减少蛋白尿,从而保护肾组织。

关键词：阿霉素慢性肾脏疾病活性维生素D_(3) 足细胞 desmin

A novel phenotype with splicing mutation identified in a Chinese family with desminopathy

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Chinese Medical Journal 2019年第2期132卷 127-134页

作者： Peng Fan Chao-Xia Lu Xue-Qi Dong Di Zhu Kun-Qi Yang Ke-Qiang Liu Di Zhang Ying Zhang Xu Meng Hui-Qiong Tan Li-Tian YU Ke-Fei DOU Ya-Xin Liu Xue Zhang Xian-Liang Zhou Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Emergency and Cdtical Care Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Background:desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations.desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia.Combined with genotype, it helps us precisely diagnose and treat for desminopathy.Methods:Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing.Phenotypes were analyzed based on clinical characteristics associated with desminopathy.Results:A splicing mutation (c.735+1G>T) in DES was detected in the proband.A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons.Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium.There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.Conclusions:We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy.Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.

关键词： desminopathy Cardiomyopathy desmin gene Splicing mutation

支气管超声内镜下良、恶性淋巴结弹性成像特点和α-SMA、desmin在淋巴结中表达水平相关性研究

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支气管超声内镜下良、恶性淋巴结弹性成像特点和α-SMA、desmin在...

作者：陈洁宁波大学

学位级别：硕士

研究目的:本研究通过分析EBUS下良、恶性淋巴结弹性成像特点,评价EBUS弹性成像对良、恶性淋巴结诊断价值。同时研究了α-SMA和desmin在良、恶性淋巴结表达程度及其与淋巴结硬度的相关性,探索α-SMA和desmin是否可能成为抗肿瘤治疗的靶... 详细信息

研究目的:本研究通过分析EBUS下良、恶性淋巴结弹性成像特点,评价EBUS弹性成像对良、恶性淋巴结诊断价值。同时研究了α-SMA和desmin在良、恶性淋巴结表达程度及其与淋巴结硬度的相关性,探索α-SMA和desmin是否可能成为抗肿瘤治疗的靶点。研究方法:运用图像处理软件计算出淋巴结在EBUS弹性成像下蓝色面积占总面积的百分比,计算良、恶性淋巴结中蓝色面积百分比是否具有差异性。运用免疫荧光染色技术检测α-SMA和desmin的表达程度,分析良、恶性淋巴结中α-SMA和desmin是否具有差异性。再将两种蛋白的表达程度和EBUS弹性成像蓝色面积百分比做出相关性分析。同时利用实时荧光定量PCR技术分析ACTA2、DES mRNA在良、恶性淋巴结中表达是否具有差异性。结果:良、恶性淋巴结在EBUS弹性成像下蓝色面积百分比存在统计学差异,恶性淋巴结的蓝色面积百分比高于良性淋巴结(P0.05)。在免疫荧光染色检测中,α-SMA在恶性淋巴结的表达高于良性淋巴结(Pdesmin在良、恶性淋巴结中的表达无统计学差异(P>0.05),α-SMA的表达和EBUS弹性成像蓝色面积百分比具有相关性(Pdesmin的表达和蓝色面积百分比无关(P>0.05)。在实时荧光定量PCR实验中,ACTA2、DES mRNA在良、恶性淋巴结的表达具有统计学差异,恶性淋巴结ACTA2 mRNA的表达高于良性淋巴结(Pdesmin在免疫荧光检测和DES mRNA在实时荧光定量PCR中结果不一致。α-SMA或许可以成为未来抗肿瘤治疗的靶点,但desmin和肿瘤之间的联系还需要继续探索。

关键词：淋巴结支气管超声内镜弹性成像 α-SMA desmin

Purinergic 2X7Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome

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Chinese Medical Journal 2018年第22期131卷 2713-2725页

作者： Xiao-Xia Hou Hong-Rui Dong Li-Jun Sun Min Yang Hong Cheng Yi-Pu Chen Division of Nephrology Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

关键词： desmin Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome Obesity-Related Glomerulopathy Podocytes Purinergic 2X7Receptor

PRIMARY CELL CULTURE FOR EMBRYONIC CARDIAC MYOCYTES OF MEXICAN AXOLOTL AND DISTRIBUTION OF desmin AND VIMENTIN

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中国组织化学与细胞化学杂志 1999年第1期8卷 113-117,131页

作者： Zhu Yongze Robert W Zajdel Margaret E Fransen Larry F Lemanski Department of Anatomy Medical College of Yangzhou UniversityYangzhou225001 China Department of Anatomy and Cell Biology State University of New YorkHealth Science Center atSyracuseSyracuseNY13210 U.S.A

desmin and vimentin are major components of intermediate filament proteins in cardiac myocytes. We developed a primary cell culture method for cardiac myocytes of axolotl embryos. Cardiac myocytes of embryonic stage 39 were cultured for 1-14 days. Myocytes showed spontaneous contractions (15-30 beats/min) after 48-72 hours in culture, round shape and large irregular projections. desmin and vimentin were observed in the cultured myocytes by means of immunofluorescent staining in combination with immunofluorescent microscopy. Immunofluorescent staining of the cultured cardiac myocytes after different lengths of time in culture(3,6,9 days) showed that vimentin staining was stronger than desmin staining during the early stages of culture (3 days). The myocytes exhibited various forms of staining, including parallel lines and interconnected networks. Some lines showed regular striation; most of the myofibrils were arranged in parallel arrays along the cell's long axis. Both desmin and vimentin in the cell appeared to encirele the Z lines and to link myofibrils laterally at the Z lines.

关键词： desmin Vimentin Cell culture Immunocytochemistry Axolotl

Protective Effects of Eplerenone on Podocyte Injury in Adriamycin Nephropathy Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第3期31卷 329-334页

作者：方展张春何方方陈珊孙希锋朱忠华刘建社孟宪芳 Department of Nephrology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Nephrology Yantai Mountain Hospital Department of Neurobiology Tongji Medical CollegeHuazhong University of Science and Technology

To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved,36 male Sprague-Dawley rats were randomly divided into control group,adriamycin nephropathy（AN） group and eplerenone-treated group（100 mg.kg-1.d-1 eplerenone）.Blood pressure,24-h urinary protein,serum potassium,sodium and creatinine were measured 28 days after adriamycin injection（a single tail intravenous injection of 6.5 mg/kg adriamycin）.The morphological changes of renal tissues were observed by light and electron microscopy.Immunohistochemistry and Western blotting were performed to examine the expression of TGF-β1 and desmin in renal cortex.The results showed that 28 days after adriamycin injection,there were no significant changes in the level of serum potassium,sodium,creatinine concentrations and blood pressure values in the rats of the three groups.Meanwhile,the 24-h proteinuria excretion in the AN group was significantly higher than that in the control group（P0.01）,but that in the eplerenone-treated group was substantially reduced when compared with that in the AN group（P0.05）.Mild mesangial cell proliferation and matrix expansion,diffuse deformation and confluence of foot processes in podocytes were found in the AN group.By contrast,rats in the eplerenone-treated group exhibited obvious attenuation of these morphological lesions.The protein expression of TGF-β1 and desmin in the AN group was markedly up-regulated in contrast to that in the control group（P0.01）,whereas that in the eplerenone-treated group was much lower than in the AN group（P0.05）.It was concluded that eplerenone may ameliorate the proteinuria and the development of pathological alteration in adriamycin-induced nephropathy presumably via the inhibition of cytokine release,and restore the morphology of podocytes independent of its blood pressure-lowing effects.

关键词： eplerenone adriamycin nephropathy podocyte TGF-β1 desmin