8 results on '"Jie Cai"'
Search Results
2. The ER stress sensor inositol-requiring enzyme 1a in Kupffer cells promotes hepatic ischemia-reperfusion injury.
- Author
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Jie Cai, Xiaoge Zhang, Peng Chen, Yang Li, Songzi Liu, Qian Liu, Hanyong Zhang, Zhuyin Wu, Ke Song, Jianmiao Liu, Bo Shan, and Yong Liu
- Subjects
- *
KUPFFER cells , *MYOCARDIAL reperfusion , *LIVER cells , *REPERFUSION injury , *NEUTROPHILS , *UNFOLDED protein response , *NITRIC-oxide synthases - Abstract
Hepatic ischemia/reperfusion (I/R) injury is an inflammation-mediated process arising from ischemia/reperfusion-elicited stress in multiple cell types, causing liver damage during surgical procedures and often resulting in liver failure. Endoplasmic reticulum (ER) stress triggers the activation of the unfolded protein response (UPR) and is implicated in tissue injuries, including hepatic I/R injury. However, the cellular mechanism that links the UPR signaling to local inflammatory responses during hepatic I/R injury remains largely obscure. Here, we report that IRE1α, a critical ER-resident transmembrane signal transducer of the UPR, plays an important role in promoting Kupffer-cell-mediated liver inflammation and hepatic I/R injury. Utilizing a mouse model in which IRE1α is specifically ablated in myeloid cells, we found that abrogation of IRE1α markedly attenuated necrosis and cell death in the liver, accompanied by reduced neutrophil infiltration and liver inflammation following hepatic I/R injury. Mechanistic investigations in mice as well as in primary Kupffer cells revealed that loss of IRE1α in Kupffer cells not only blunted the activation of the NLRP3 inflammasome and IL-1β production, but also suppressed the expression of the inducible nitric oxide synthase (iNos) and proinflammatory cytokines. Moreover, pharmacological inhibition of IRE1α's RNase activity was able to attenuate inflammasome activation and iNos expression in Kupffer cells, leading to alleviation of hepatic I/R injury. Collectively, these results demonstrate that Kupffer cell IRE1α mediates local inflammatory damage during hepatic I/R injury. Our findings suggest that IRE1α RNase activity may serve as a promising target for therapeutic treatment of ischemia/reperfusion-associated liver inflammation and dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
3. Structural and Functional Studies of a Newly Grouped Haloquadratum walsbyi Bacteriorhodopsin Reveal the Acid-resistant Light-driven Proton Pumping Activity
- Author
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Andrew H.-J. Wang, Hsiu-Pin Yi, Min-Feng Hsu, Chii Shen Yang, Hsu Yuan Fu, and Chun-Jie Cai
- Subjects
Cytoplasm ,Optics and Photonics ,genetic structures ,Light ,Trimer ,Crystallography, X-Ray ,Protein Engineering ,Biochemistry ,membrane protein ,Phylogeny ,biology ,ATP synthase ,bacteriorhodopsin ,Chemistry ,Hydrogen bond ,Haloquadratum walsbyi ,spectral-tuning ,Hydrogen-Ion Concentration ,Proton pump ,Bacteriorhodopsins ,Protein Structure and Folding ,site-directed mutagenesis ,Protons ,inorganic chemicals ,crystal structure ,Archaeal Proteins ,Molecular Sequence Data ,Static Electricity ,natural sciences ,structure ,Amino Acid Sequence ,Molecular Biology ,Ion transporter ,lipid cubic phase ,Ion Transport ,Sequence Homology, Amino Acid ,organic chemicals ,Hydrogen Bonding ,Bacteriorhodopsin ,Cell Biology ,biology.organism_classification ,Archaea ,Crystallography ,rhodopsin ,proton pump ,biological sciences ,Mutation ,Mutagenesis, Site-Directed ,Biophysics ,biology.protein ,Spectrophotometry, Ultraviolet - Abstract
Background: Most bacteriorhodopsins demonstrate red-shifted spectrum in acidic condition. Results: Structures of Haloquadratum walsbyi bacteriorhodopsin explain stable action spectra from pH 2 to 8. Conclusion: The extracellular hydrogen-bonding network assists in the maintenance of protonation status in the Haloquadratum walsbyi bacteriorhodopsin retinal-binding pocket. Significance: A bacteriorhodopsin subfamily has a stable optical property, and its structure is useful for protein engineering in optogenetic tools., Retinal bound light-driven proton pumps are widespread in eukaryotic and prokaryotic organisms. Among these pumps, bacteriorhodopsin (BR) proteins cooperate with ATP synthase to convert captured solar energy into a biologically consumable form, ATP. In an acidic environment or when pumped-out protons accumulate in the extracellular region, the maximum absorbance of BR proteins shifts markedly to the longer wavelengths. These conditions affect the light-driven proton pumping functional exertion as well. In this study, wild-type crystal structure of a BR with optical stability under wide pH range from a square halophilic archaeon, Haloquadratum walsbyi (HwBR), was solved in two crystal forms. One crystal form, refined to 1.85 Å resolution, contains a trimer in the asymmetric unit, whereas another contains an antiparallel dimer was refined at 2.58 Å. HwBR could not be classified into any existing subgroup of archaeal BR proteins based on the protein sequence phylogenetic tree, and it showed unique absorption spectral stability when exposed to low pH values. All structures showed a unique hydrogen-bonding network between Arg82 and Thr201, linking the BC and FG loops to shield the retinal-binding pocket in the interior from the extracellular environment. This result was supported by R82E mutation that attenuated the optical stability. The negatively charged cytoplasmic side and the Arg82–Thr201 hydrogen bond may play an important role in the proton translocation trend in HwBR under acidic conditions. Our findings have unveiled a strategy adopted by BR proteins to solidify their defenses against unfavorable environments and maintain their optical properties associated with proton pumping.
- Published
- 2015
4. MicroRNA Cluster 302–367 Enhances Somatic Cell Reprogramming by Accelerating a Mesenchymal-to-Epithelial Transition
- Author
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Duanqing Pei, Wenbo Liu, Liwen Niu, Ruosi Zhang, Shipeng Feng, Liangxue Lai, Jie Cai, Maikun Teng, Xichen Bao, Jiayan Wu, Miguel A. Esteban, Baoming Qin, Longqi Liu, Athanasios Zovoilis, Baojian Liao, Yanting Xue, Xiangpeng Guo, and Biliang Zhang
- Subjects
Male ,Somatic cell ,Induced Pluripotent Stem Cells ,Biology ,Biochemistry ,Mesoderm ,Kruppel-Like Factor 4 ,Mice ,SOX2 ,Transforming Growth Factor beta ,Cell Adhesion ,Animals ,Induced pluripotent stem cell ,Molecular Biology ,Cell potency ,Induced stem cells ,Stem Cells ,Epithelial Cells ,Cell Biology ,Fibroblasts ,Cell biology ,MicroRNAs ,Phenotype ,KLF4 ,Female ,Stem cell ,Reprogramming - Abstract
MicroRNAs (miRNAs) are emerging critical regulators of cell function that frequently reside in clusters throughout the genome. They influence a myriad of cell functions, including the generation of induced pluripotent stem cells, also termed reprogramming. Here, we have successfully delivered entire miRNA clusters into reprogramming fibroblasts using retroviral vectors. This strategy avoids caveats associated with transient transfection of chemically synthesized miRNA mimics. Overexpression of 2 miRNA clusters, 106a-363 and in particular 302-367, allowed potent increases in induced pluripotent stem cell generation efficiency in mouse fibroblasts using 3 exogenous factors (Sox2, Klf4, and Oct4). Pathway analysis highlighted potential relevant effectors, including mesenchymal-to-epithelial transition, cell cycle, and epigenetic regulators. Further study showed that miRNA cluster 302-367 targeted TGFβ receptor 2, promoted increased E-cadherin expression, and accelerated mesenchymal-to-epithelial changes necessary for colony formation. Our work thus provides an interesting alternative for improving reprogramming using miRNAs and adds new evidence for the emerging relationship between pluripotency and the epithelial phenotype.
- Published
- 2011
5. Induced Pluripotent Stem Cells Can Be Used to Model the Genomic Imprinting Disorder Prader-Willi Syndrome.
- Author
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Jiayin Yang, Jie Cai, Ya Zhang, Xianming Wang, Wen Li, Jianyong Xu, Feng Li, Xiangpeng Guo, Kang Deng, Mei Zhong, Yonglong Chen, Liangxue Lai, Duanqing Pei, and Esteban, Miguel A.
- Subjects
- *
EMBRYONIC stem cells , *INBORN errors of metabolism , *LESCH-Nyhan syndrome , *GENETICS , *GENE expression , *NUCLEIC acids - Abstract
The recent discovery of induced pluripotent stem cell (iPSC) technology provides an invaluable tool for creating in vitro representations of human genetic conditions. This is particularly relevant for those diseases that lack adequate animal models or where the species comparison is difficult, e.g. imprinting diseases such as the neurogenetic disorder Prader-Willi syndrome (PWS). However, recent reports have unveiled transcriptional and functional differences between iPSCs and embryonic stem cells that in cases are attributable to imprinting errors. This has suggested that human iPSCs may not be useful to model genetic imprinting diseases. Here, we describe the generation of iPSCs from a patient with PWS bearing a partial translocation of the paternally expressed chromosome 15q11-q13 region to chromosome 4. The resulting iPSCs match all standard criteria of bona fide reprogramming and could be readily differentiated into tissues derived from the three germ layers, including neurons. Moreover, these iPSCs retain a high level of DNA methylation in the imprinting center of the maternal allele and show concomitant reduced expression of the disease-associated small nucleolar RNA HBII-85/SNORD116. These results indicate that iPSCs may be a useful tool to study PWS and perhaps other genetic imprinting diseases as well. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
6. Structural and Functional Studies of a Newly Grouped Haloquadratum walsbyi Bacteriorhodopsin Reveal the Acid-resistant Light-driven Proton Pumping Activity.
- Author
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Min-Feng Hsu, Hsu-Yuan Fu, Chun-Jie Cai, Hsiu-Pin Yi, Chii-Shen Yang, and Wang, Andrew H.-J.
- Subjects
- *
BACTERIORHODOPSIN , *PROTEIN structure , *PROTON pumps (Biology) , *ADENOSINE triphosphatase , *SOLAR energy - Abstract
Retinal bound light-driven proton pumps are widespread in eukaryotic and prokaryotic organisms. Among these pumps, bacteriorhodopsin (BR) proteins cooperate with ATP synthase to convert captured solar energy into a biologically consumable form, ATP. In an acidic environment or when pumped-out protons accumulate in the extracellular region, the maximum absorbance of BR proteins shifts markedly to the longer wavelengths. These conditions affect the light-driven proton pumping functional exertion as well. In this study, wild-type crystal structure of a BR with optical stability under wide pH range from a square halophilic archaeon, Haloquadratum walsbyi (HwBR), was solved in two crystal forms. One crystal form, refined to 1.85 Å resolution, contains a trimer in the asymmetric unit, whereas another contains an antiparallel dimer was refined at 2.58 Å. HwBR could not be classified into any existing subgroup of archaeal BR proteins based on the protein sequence phylogenetic tree, and it showed unique absorption spectral stability when exposed to low pH values. All structures showed a unique hydrogen-bonding network between Arg82 and Thr201, linking the BC and FG loops to shield the retinal-binding pocket in the interior from the extracellular environment. This result was supported by R82E mutation that attenuated the optical stability. The negatively charged cytoplasmic side and the Arg82-Thr201 hydrogen bond may play an important role in the proton translocation trend in HwBR under acidic conditions. Our findings have unveiled a strategy adopted by BR proteins to solidify their defenses against unfavorable environments and maintain their optical properties associated with proton pumping. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
7. Phosphorylation at Ser724 of the ER stress sensor IRE1α governs its activation state and limits ER stress–induced hepatosteatosis.
- Author
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Yang Li, Shijia Huang, Jingsi Wang, Jianli Dai, Jie Cai, Shuai Yan, Zhiliang Huang, Shengqi He, Ping Wang, Jianmiao Liu, and Yong Liu
- Subjects
- *
KINASES , *UNFOLDED protein response , *PHOSPHORYLATION , *MEMBRANE proteins , *CARRIER proteins , *FATTY liver - Abstract
Inositol-requiring enzyme 1 (IRE1) is an evolutionarily conserved sensor of endoplasmic reticulum (ER) stress and mediates a key branch of the unfolded protein response in eukaryotic cells. It is an ER-resident transmembrane protein that possesses Ser/Thr protein kinase and endoribonuclease (RNase) activities in its cytoplasmic region. IRE1 is activated through dimerization/oligomerization and autophosphorylation at multiple sites, acting through its RNase activity to restore the functional capacity of the ER. However, it remains poorly defined in vivo how the autophosphorylation events of endogenous IRE1 govern its dynamic activation and functional output. Here, we generated a mouse model harboring a S724A knock-in mutation (Ern1S724A/S724A) and investigated the importance of phosphorylation at Ser724 within the kinase activation loop of murine IRE1α. We found that in mouse embryonic fibroblast cells and in primary hepatocytes, S724A mutation resulted in markedly reduced IRE1α autophosphorylation in parallel with blunted activation of its RNase activity to catalyze X-box binding protein 1 (Xbp1) mRNA splicing. Furthermore, ablation of IRE1α phosphorylation at Ser724 exacerbated ER stress–induced hepatic steatosis in tunicamycin- treated Ern1S724A/S724A mice. This was accompanied by significantly decreased hepatic production of spliced XBP1 protein but increased CCAAT-enhancer–binding protein homologous protein (CHOP) level, along with suppressed expression of key metabolic regulators of fatty acid β-oxidation and lipid secretion. These results demonstrate a critical role of phosphorylation at Ser724 of IRE1α in dynamically controlling its kinase activity, and thus its autophosphorylation state, which is coupled to activation of its RNase activity in counteracting hepatic steatosis under ER stress conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. MicroRNA Cluster 302-367 Enhances Somatic Cell Reprogramming by Accelerating a Mesenchymal-to- Epithelial Transition.
- Author
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Baojian Liao, Xichen Bao, Longqi Liu, Shipeng Feng, Zovoilis, Athanasios, Wenbo Liu, Yanting Xue, Jie Cai, Xiangpeng Guo, Baoming Qin, Zhang, Ruosi, Jiayan Wu, Liangxue Lai, Maikun Teng, Liwen Niu, Biliang Zhang, Esteban, Miguel A., and Duanqing Pei
- Subjects
- *
FIBROBLASTS , *STEM cells , *GENETIC transformation , *GENOTYPE-environment interaction , *NUCLEIC acids - Abstract
MicroRNAs (miRNAs) are emerging critical regulators of cell function that frequently reside in clusters throughout the genome. They influence a myriad of cell functions, including the generation of induced pluripotent stem cells, also termed reprogramming. Here, we have successfully delivered entire miRNA clusters into reprogramming fibroblasts using retroviral vectors. This strategy avoids caveats associated with transient transfection of chemically synthesized miRNA mimics. Overexpression of 2 miRNA clusters, 106a-363 and in particular 302-367, allowed potent increases in induced pluripotent stem cell generation efficiency in mouse fibroblasts using 3 exogenous factors (Sox2, Klf4, and Oct4). Pathway analysis highlighted potential relevant effectors, including mesenchymal-to-epithelial transition, cell cycle, and epigenetic regulators. Further study showed that miRNA cluster 302-367 targeted TGFβ receptor 2, promoted increased E-cadherin expression, and accelerated mesenchymal-to-epithelial changes necessary for colony formation. Our work thus provides an interesting alternative for improving reprogramming using miRNAs and adds new evidence for the emerging relationship between pluripotency and the epithelial phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
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