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Mannose metabolism normalizes gut homeostasis by blocking the TNF-α-mediated proinflammatory circuit

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Cellular & Molecular Immunology 2023年第2期20卷 119-130页

作者： Peng Xiao Ziwei Hu Jiaheng Lang Tianyuan Pan Randall Tyler Mertens Huilun Zhang ke Guo Manlu Shen Hongqiang Cheng Xue Zhang Qian Cao yuehai ke Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouChina Department of Pathology and Pathophysiology and Department of Gastroenterology at Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouChina Immunological Disease Research Center Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouChina key Laboratory for Immunity and Inflammatory Diseases of Zhejiang Province HangzhouChina Department of Pathology and Pathophysiology Zhejiang University School of MedicineHangzhouChina Department of General Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of Immunology Harvard Medical SchoolBostonMAUSA Zhejiang Laboratory for Systems and Precision Medicine Zhejiang University Medical CenterHangzhouChina

Mannose is a naturally occurring sugar widely consumed in the daily diet;however,mechanistic insights into how mannose metabolism affects intestinal inflammation remain ***,we reported that mannose supplementation ameliorated colitis development and promoted colitis ***-secreted inflammatory cytokines,particularly TNF-α,induced pathological endoplasmic reticulum stress(ERS)in intestinal epithelial cells(IECs),which was prevented by mannose via normalization of protein *** preserving epithelial integrity,mannose reduced the inflammatory activation of colonic *** the other hand,mannose directly suppressed macrophage TNF-αproduction translationally by reducing the glyceraldehyde 3-phosphate level,thus promoting GAPDH binding to TNF-α***,we found dysregulated mannose metabolism in the colonic mucosa of patients with inflammatory bowel ***,we revealed that activating PMM2 activity with epalrestat,a clinically approved drug for the treatment of diabetic neuropathy,elicited further sensitization to the therapeutic effect of ***,mannose metabolism prevents TNF-α-mediated pathogenic crosstalk between IECs and intestinal macrophages,thereby normalizing aberrant immunometabolism in the gut.

关键词： Colitis Mannose Macrophages Intestinal epithelial cells TNF-alpha Endoplasmic reticulum stress

Tyrosine phosphatase Shp2 regulates pi 15RhoGEF/Rhodependent dendritic cell migration

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Cellular & Molecular Immunology 2021年第3期18卷 755-757页

作者： Yun Xu Yun Zhang Yanyan Yang Yanqi Liu Qiaoying Tian Pan Liu Zhifan Ding Hongqiang Cheng Xue Zhang yuehai ke Department of Pathology and Pathophysiology Zhejiang University School of MedicineHangzhou 310058 ZhejiangChina lnstitute of Basic Research in Clinical Medicine College of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhouChina Department of Pathology and Pathophysiology and Department of Respiratory Medicine at Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310058 ZhejiangChina

The orchestrated migration of dendritic cells(DCs)to secondary lymphoid organs relies on C-C chemokine receptor type 7(CCR7)and its ligand C-C motif chemokine ligand 19(CCL19),and DC migration to lymph nodes is crucia... 详细信息

关键词： organs CCR7 Shp2

Disruption of Shp2 destabilizes Hes-1/Stat-3 complex in intestinal epithelia,contributing to enhance self-renewal capacity and impair differentiation in crypt niche

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Disruption of Shp2 destabilizes Hes-1/Stat-3 complex in inte...

生命的分子机器及其调控网络——2012年全国生物化学与...

作者： Qiu Gui Xue Zhang yuehai ke Department of Pathology and Pathophysiology and Program in Molecular Cell BiologyZhejiang University School of Medicine

The human gene Ptpn11 encoding the Src-homology 2 domain-containing phosphatase 2(SHP2),has opposite self-renewal regulation of Shp2 for embryonic stem cells and neural stem ***2 may act as a proto-oncogene since dominantly activating mutations have been detected in several types of leukemia,while it has a tumor-suppressor function in hepatocellular carcinogenesis. Here we report a differentiation-inhibitor and tu-mor-suppressor function of *** epithelium-specific deletion of Shp2 promotes the Notch and JAK/STAT signalling pathways fulfilling overlapping roles in growth and dif-ferentiation regulation via

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Tyrosine phosphatase Shp2 acts as an antifibrotic regulator in pulmonary fibrosis

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Tyrosine phosphatase Shp2 acts as an antifibrotic regulator ...

2017中国长三角遗传学大会

作者： Jiaqi Xu Zhang Xue ke yuehai Department of Pathology Sir Run Run Shaw HospitalZhejiang University School of Medicine Department of Pathology and Pathophysiology and Program in Molecular Cell Biology Zhejiang University School of Medicine Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases

Idiopathic pulmonary fibrosis(IPF) is a chronic interstitial disease of unknown etiology and refractory to current therapeutic options,which is characterized by alveolar inflammation,distorted alveolar architecture and exaggerated collagen ***,the mechanisms underlying this devastating progression remain ***2 is a cytoplasmic tyrosine phosphatase encoded by PTPNll that contains two Src homology(SH2) domains and one catalytic protein tyrosine phosphatase(PTP)***2 integrates multiple signaling pathways involving a variety of physiological ***,little is known about the role of Shp2 in interstitial lung disease,and genetic models have not yet been described Using a combined Cre-loxP-mediated inducible knockout approach,we generated a triple-transgenic Shp2-knockout(SP-C-rtTA/(tetO)7-Cre)/Shp2 f/f) mice in which Shp2 gene was inactivated in alveoli epithelia after Dox *** transgenic mouse model revealed that ablation of Shp2 in alveoli epithelia led to reduced surfactant protein production,impaired alveolar structures and lung mechanics,and eventually the development of spontaneous interstitial ***,selective disruption of Shp2(LysMCre:Shp2) in macrophages augmented IL-4-mediated M2 *** LysMCre:Shp2 mice exhibited normal lung histology at up to 6-8 weeks of age,fibrotic lesions in Shp2-knockout mice were severely aggravated in a bleomycin-induced lung fibrosis *** genetic evidences indicate that Shp2 acts as an anti-fibrotic gene in ***,recent clinical study validate that Shp2 expression is decreased in IPF patients,supporting the pivotal function of Shp2 in *** addition,we have introduced Sftpc-CreETR2/Shp2 mice to further optimize this genetic *** will be administered to induce Cre expression and shp2 gene inactivation in alveoli epithelia which genetic phenotype will be studied in our future *** summary,our findings

关键词： pulmonary fibrosis Shp2 mouse model

Docking protein Gab2 regulates mucous hypersecretion and goblet cell hyperplasia through TYK2/STAT6 pathway

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Docking protein Gab2 regulates mucous hypersecretion and gob...

生命的分子机器及其调控网络——2012年全国生物化学与分子生物学学术大会

作者： Yun Zhang Xue Zhang yuehai ke Department of Pathology and Pathophysiology and Program in Molecular Cell BiologyZhejiang University School of Medicine

Goblet cell hyperplasia(GCH) and mucous hypersecretion are common pathological fea-tures of chronic pulmonary diseases including asthma,chronic obstructive pulmonary dis-ease(COPD),lung cancer and cystic *** numerous studies,the molecular basis for this condition remains ***,we show a novel role for docking protein Gab2(Grb2-associated binder 2, Gab2) in the regulation of airway mucous cell ***2 is a member of the Dos/Gab subfamily scaffolding molecules and plays important roles in regulating growth,differentiation and *** this study,we found mat an elev-ated level of Gab2

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Y-chromosome evidence for no independent origin of modern human in China

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Chinese Science Bulletin 2001年第11期46卷 935-937页

作者： ke yuehai SU Bing LI Hongyu CHEN Lifeng QI Chunjian GUO Xinjun HUANG Wei JIN Jianzhong LU Daru JIN Li Institute of Genetics and Morgan-Tan International Center for Life Science Fudan UniversityShanghai 200433China Kunming Institute of Zoology Chinese Academy of SciencesKunming 650031China Human Genetics Center University of Texas-HoustonHouston 77225USA Department of Biotechnology Suzhou UniversitySuzhou 215007China TSBIO Science&Technology Co. LtdHangzhou 310013China National Human Genome Center at Shanghai Shanghai 201203China

East Asia is one of the few regions in the world where a large number of human fossils have been unearthed. The continuity of hominid fossils in East Asia, particularly in China has been presented as strong evidence supporting an independent origin of modern humans in this area. To search for such evidence of a possible independent origin of modern humans in China, a total of 9988 male individuals were sampled across China. Three Y-chromosome biallelic markers (M89, M130 and YAP), which were located at the non-re-combinant region of Y-chromosome, were typed among the samples. Our result showed that all the individuals carry a mutation at one of the three loci. The three mutations (M89T, M130T, YAP+) coalesce to another mutation (M168T), which was originally derived from Africa about 31000 to 79000 years ago. In other words, all Y-chromosome samples from China, with no exception, were originally derived from a lineage of African origin. Hence, we conclude that even a very minor contribution of in situ hominid origin in China cannot be supported by the Y-chromosome evidence.

关键词： Y-chromosome haplotype SNPs modern human origin Chinese.

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高考数学创新性考查要求的落实路径探析

中国考试 2021年第1期 63-69页

作者：柯跃海福建师范大学数学与信息学院福州350117

创新性作为高考评价体系中“四翼”的重要组成部分,是评价学生素质达成度的重要参照。落实高考数学创新性考查要求,要聚焦与创新关联密切的学科素养和关键能力,遵循选拔性、整体性和导向性原则,立足数学知识或方法的即用、知用、善用能... 详细信息

创新性作为高考评价体系中“四翼”的重要组成部分,是评价学生素质达成度的重要参照。落实高考数学创新性考查要求,要聚焦与创新关联密切的学科素养和关键能力,遵循选拔性、整体性和导向性原则,立足数学知识或方法的即用、知用、善用能力发展水平的检测,为高考“服务选才”功能的落实和“引导教学”功能的发挥筑牢着力点和支撑点。

关键词：高考高考数学高考评价体系创新性学科素养关键能力

Macrophage lacking Shp2 promotes fibrosis in an alternatively-activated manner

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Macrophage lacking Shp2 promotes fibrosis in an alternativel...

生命的分子机器及其调控网络——2012年全国生物化学与分子生物学学术大会

作者： Bo Tao Wei Jin Xue Zhang yuehai ke Department of Pathology and Pathophysiology and Program in Molecular Cell BiologyZhejiang University School of Medicine

Alternative macrophage activation(M2) is critical in host defense against parasites and take a protective role in inflammatory bowel disease,but contributes to pathology in asthma and solid *** mechanisms underlying macrophage programming are only partially understood and little is known about their amenability to manipulation in patho-physiological ***2, a ubiquitously expressed cytoplasmic tyrosine phosphata-se,has been previously demonstrated to be a critical signal transducer

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Roles of scaffolding protein Gab1 in regulation of myeloid dendritic cell-mediated allergic asthma

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Roles of scaffolding protein Gab1 in regulation of myeloid d...

中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Yun Zhang Yun Xu Dong Cen Jiaqi Xu Xue Zhang yuehai ke zhejang University Zhejang University

Scaffolding proteins Gab1 is ubiquitously expressed and belongs to the GAB family(GABs),which integrates multiple signal *** protein family has recently attracted interestthat genetic variants of human GAB1 are considered a risk factor for *** previousresearch has revealed a novel function of Gab2 in mediating mucin gene expression andGoblet cell hyperplasia(GCH),which is an important process in ***,the functionof Gab1 in asthma remains *** asthma exacerbated patients,we found a prominentelevated level of Gab1 in peripheral blood monouclear cells compared to that of ***,we generated conditional Gab1 deletion mice in myeloid cells(Gab1 KO mice)to determinate physiological the role of Gab1 in *** histologyand mucus metaplasia indicated that disruption of Gab1 in dendritic cells(DCs)leads to alleviatedasthmatic *** investigation showed that loss of Gab1results inimpaired DC migration to lymph node,while has no influences on DC maturation、antigenuptake and ***,Gab1 is essentially involved in CCL19-mediatedAKT ***,these finding has characterized a novel of Gab1 in mediating DCmigration and that deregulation of Gab1 signal in lungs predisposes asthmatic inflammation.

关键词： Gab1 dendritic cell allergic asthma