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Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition

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Chinese Journal of Natural Medicines 2024年第1期22卷 31-46页

作者： QU Jiaorong XUE Xiaoyong WANG Zhixing MA Zhi JIA Kexin LI Fanghong ZHANG Yinhao WU Ruiyu ZHOU Fei ZHAO Piwen LI Xiaojiaoyang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional Chinese medicine(TCM)formula,is known for treating gynecological diseases and liver fibrosis.Our previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis.However,the mechanisms by which SWT influences H19 remain unclear.Thus,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver.Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver.Notably,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular injury.This modulation collectively led to reduced ECM deposition.Through extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory pathways.Meanwhile,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver fibrosis.However,these protective effects of SWT were diminished with the overexpression of H19 in vivo.In conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

关键词： Liver fibrosis LncRNA H19 Si-Wu-Tang miRNAs cytoskeleton ECM deposition

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How do neurons age?A focused review on the aging of the microtubular cytoskeleton

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Neural Regeneration Research 2024年第9期19卷 1899-1907页

作者： Brad Richardson Thomas Goedert Shmma Quraishe Katrin Deinhardt Amritpal Mudher School of Biological Sciences University of SouthamptonSouthamptonUK Institute of Developmental and Regenerative Medicine University of OxfordOxfordUK

Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and brain

关键词： age-related changes aging cytoskeleton microtubules neuronal morphology

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Aluminum exposure impairs oocyte quality via subcellular structure disruption and DNA damage-related apoptosis in mice

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Journal of Environmental Sciences 2024年第5期139卷 308-319页

作者： Hongge Li Jingcai Liu Weihua Nong Mengying Shen Sheng Dou Shaochen Sun Junli Wang The Affiliated Hospital of Youjiang Medical University for Nationalities Guangxi 533000China College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China School of Medical Laboratory Youjiang Medical University for NationalitiesGuangxi 533000China Industrial College of Biomedicine and Health Industry Youjiang Medical University for NationalitiesGuangxi 533000China Reproductive Medicine Guangxi Medical and Health Key Discipline Construction ProjectThe Affiliated Hospital of Youjiang Medical University for NationalitiesGuangxi 533000China

Aluminum(Al)can lead to an exposure of creature in varieties ways for its universality,and it could disturb normal physiological metabolism,with the damage to multisystem including reproduction.Since the oocyte quality is critical for female reproduction,we inspected the toxicity of Al on mouse oocyte maturation.We constructed in vitro exposure mouse model,and we found that 5 mmol/L Al had adverse effects on oocyte maturation by impairing organelle and cytoskeleton.Aberrant spindle and misaligned chromosomes which might be considered to be caused by elevated levels of acetylation,as well as abnormal distribution of actin dynamics could hinder normal meiosis of oocytes.Organelle dysfunction indicated that Al affected proteins synthesis,transport and digestion,which would further damage oocyte maturation.In order to explore the mechanism of Al toxicity,our further investigation demonstrated that Al caused mitochondrial dysfunction and imbalance calcium homeostasis,resulting in limited energy supply.Moreover,high level of reactive oxygen species,DNA damage and apoptosis caused by oxidative stress were also the manifestation of Al toxicity on oocytes.In conclusion,our study provided the evidence that Al exposure affected oocyte quality through its effects on spindle organization,actin dynamics,organelle function and the induction of DNA damage-related apoptosis with mouse model.

关键词： Aluminum Oocyte cytoskeleton Organelle DNA damage

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GhWDL3 is involved in the formation and development of fiber cell morphology in upland cotton(Gossypium hirsutum L.)

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Journal of Cotton Research 2024年第1期7卷 58-68页

作者： CHEN Baojun TIAN Zailong FU Guoyong ZHANG Ai SUN Yaru WANG Jingjing PAN Zhaoe LI Hongge HU Daowu XIA Yingying HE Shoupu DU Xiongming Zhengzhou Research Base National Key Laboratory of Cotton Bio-Breeding and Integrated UtilizationZhengzhou UniversityZhengzhouHenan 450001China National Key Laboratory of Cotton Bio-Breeding and Integrated Utilization Institute of Cotton ResearchChinese Academy of Agricultural SciencesAnyangHenan 455000China National Supercomputing Center in Zhengzhou Zhengzhou UniversityZhengzhouHenan 450001China

Background Cotton fiber is a model tissue for studying microtubule-associated proteins(MAPs).The Xklp2(TPX2)proteins that belong to the novel MAPs member mainly participate in the formation and development of microtubule(MT).However,there is a lack of studies concerning the systematic characterization of the TPX2 genes family in cotton.Therefore,the identification and portrayal of G.hirsutum TPX2 genes can provide key targets for molecular manipula-tion in the breeding of cotton fiber improvement.Result In this study,TPX2 family genes were classified into two distinct subclasses TPXLs and MAP genes WAVE DAMP-ENED2-LIKE(WDLs)and quite conservative in quantity.GhWDL3 was significantly up-regulated in 15 days post anthe-sis fibers of ZRI-015(an upland cotton with longer and stronger fiber).GhWDL3 promotes all stem hairs to become straight when overexpressed in Arabidopsis,which may indirectly regulate cotton fiber cell morphology during fiber development.Virus induced gene silencing(VIGS)results showed that GhWDL3 inhibited fiber cell elongation at fiber development periods through regulating the expression of cell wall related genes.Conclusion These results reveal that GhWDL3 regulated cotton fiber cell elongation and provide crucial information for the further investigation in the regulatory mechanisms/networks of cotton fiber length.

关键词： Upland cotton GhWDL3 Fiber length TPX2 cytoskeleton Microtubule-associated proteins(MAPs)

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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical Sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular Cell Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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Single-cell manipulation by two-dimensional micropatterning

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 45-59页

作者： Xuehe Ma Haimei Zhang Shiyu Deng Qiushuo Sun Qingsong Hu Yuhang Pan Fen Hu Imshik Lee Fulin Xing Leiting Pan The Key Laboratory of Weak-Light Nonlinear Photonics of Education Ministry School of Physics and TEDA Institute of Applied Physics Nankai University Tianjin 300071P.R.China State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for Cell Responses College of Life Sciences Nankai University Tianjin 300071P.R.China Collaborative Innovation Center of Extreme Optics Shanxi University TaiyuanShanxi 030006P.R.China Shenzhen Research Institute of Nankai University Shenzhen Guangdong 518083P.R.China

Cells are highly sensitive to their geometrical and mechanical microenvironment that directly regulate cell shape,cytoskeleton and organelle,as well as the nucleus morphology and genetic expression.The emerging two-dimensional micropatterning techniques offer powerful tools to construct controllable and well-organized microenvironment for single-cell level investigations with qualitative analysis,cellular standardization,and in vivo environment mimicking.Here,we provide an overview of the basic principle and characteristics of the two most widely-used micropatterning techniques,including photolithographic micropatterning and soft lithography micropatterning.Moreover,we summarize the application of micropatterning technique in controlling cytoskeleton,cell migration,nucleus and gene expression,as well as intercellular communication.

关键词： Two-dimensional micropatterning cytoskeleton cell migration extracellular matrix intercellular communication gene expression

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The unconventional prefoldin RPB5 interactor mediates the gravitropic response by modulating cytoskeleton organization and auxin transport in Arabidopsis

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Journal of Integrative Plant Biology 2022年第10期64卷 1916-1934页

作者： Yi Yang Fang Liu Le Liu Mingyue Zhu Jinfeng Yuan Yan‐Xia Mai Jun‐Jie Zou Jie Le Yonghong Wang Klaus Palme Xugang Li Yong Wang Long Wang State Key Laboratory of Crop Biology College of Life SciencesShandong Agricultural UniversityDaizong Street 61Tai'an 271018China Shandong Provincial Key Laboratory of Biophysics Institute of BiophysicsDezhou UniversityDezhou 253023China Sino‐German Joint Research Center on Agricultural Biology College of Life SciencesShandong Agricultural UniversityDaizong Street 61Tai'an 271018China Faculty of Biology Institute of Biology II/Molecular Plant PhysiologyAlbert‐Ludwigs‐University of FreiburgSchänzlestrasse 1Freiburg D‐79104Germany National Key Laboratory of Plant Molecular Genetics(NKLPMG) CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and Ecology(SIPPE)Chinese Academy of Sciences(CAS)Shanghai 200032China Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China Key Laboratory of Plant Molecular Physiology CAS Center for Excellence in Molecular Plant SciencesInstitute of BotanyChinese Academy of SciencesBeijing 100093China University of Chinese Academy of Sciences Beijing 100049China

Gravity-induced root curvature involves the asymmetric distribution of the phytohormone auxin.This response depends on the concerted activities of the auxin transporters such as PIN-FORMED(PIN)proteins for auxin efflux and AUXIN RESISTANT 1(AUX1)for auxin influx.However,how the auxin gradient is established remains elusive.Here we identified a new mutant with a short root,strong auxin distribution in the lateral root cap and an impaired gravitropic response.The causal gene encoded an Arabidopsis homolog of the human unconventional prefoldin RPB5 interactor(URI).At URI interacted with prefoldin 2(PFD2)and PFD6,twoβ-type PFD members that modulate actin and tubulin patterning in roots.The auxin reporter DR5_(rev):GFP showed that asymmetric auxin redistribution after gravistimulation is disordered in aturi-1 root tips.Treatment with the endomembrane protein trafficking inhibitor brefeldin A indicated that recycling of the auxin transporter PIN2 is disrupted in aturi-1 roots as well as in pfd mutants.We propose that At URI cooperates with PFDs to recycle PIN2and modulate auxin distribution.

关键词： Arabidopsis auxin cytoskeleton PIN2 prefoldin(PFD) unconventional prefoldin RPB5 interactor(URI)

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Study of cytoskeleton from microscopic point of view:Our experience

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BIOCELL 2022年第4期46卷 881-884页

作者： CINZIA SIGNORINI GIULIA COLLODEL ELENA MORETTI Department of Molecular and Developmental Medicine of University of Siena SienaI-53100Italy

The manuscript deals with our studies and experiences in the assessment of cytoskeleton in different cellular models and situations.The immunofluorescent study of several cytoskeletal proteins was relevant in the evaluation of a therapy for osteoarthritis,in case of alkaptonuria and in testing the efficacy of docetaxel in neuroblastoma cancer cells leading to apoptosis.A relevant part of our experience focus on the study of cytoskeleton in seminiferous epithelium and spermatozoa,identifying alterations affecting blood-testis barrier after a silver nanoparticle treatment,chromosomal segregation in case of varicocele,sperm motility and diagnosing systematic sperm defects as“Primary ciliary dyskinesia”and“Dysplasia of the fibrous sheath”.The evaluation of cytoskeleton represents a specific and sensitive analysis in establishing the health status of different cells.

关键词： cytoskeleton Environment Immunocytochemistry Pathological condition

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cytoskeleton and Early Development in Fucoid Algae

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Journal of Integrative Plant Biology 2007年第8期49卷 1192-1198页

作者： Sherryl R.Bisgrove Simon Fraser University Department of Biological Sciences8888 University DriveBurnaby B.C.Canada V5A 1S6

Cell polarization and asymmetric cell divisions play important roles during development in many multicellular eukaryotes. Fucoid algae have a long history as models for studying early developmental processes, probably because of the ease with which zygotes can be observed and manipulated in the laboratory. This review discusses cell polarization and asymmetric cell divisions in fucoid algal zygotes with an emphasis on the roles played by the cytoskeleton.

关键词： actin asymmetric cell division cell polarization cytoskeleton early development fucoid algae microtubules zygote

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O-GlcNAcylation regulates phagocytosis by promoting Ezrin localization at the cell cortex

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Journal of Genetics and Genomics 2023年第7期50卷 486-496页

作者： Song Yang Hanyu Liu Hua Ni Lingyu Jiang Mulin Yang Quan Chen Jun Zhou Fan Yu State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for Cell ResponsesTianjin Key Laboratory of Protein ScienceHaihe Laboratory of Cell EcosystemCollege of Life SciencesNankai UniversityTianjin 300071China CNBG-Nankai Joint Research Center Nankai UniversityTianjin 300071China College of Life and Geographic Sciences Kashi UniversityXinjiang 844000China

O-GlcNAcylation is a post-translational modification that serves as a cellular nutrient sensor and participates in multiple physiological and pathological processes.However,it remains uncertain whether O-GlcNAcylation is involved in the regulation of phagocytosis.Here,we demonstrate a rapid increase in protein OGlcNAcylation in response to phagocytotic stimuli.Knockout of the O-GlcNAc transferase or pharmacological inhibition of O-GlcNAcylation dramatically blocks phagocytosis,resulting in the disruption of retinal structure and function.Mechanistic studies reveal that the O-GlcNAc transferase interacts with Ezrin,a membrane-cytoskeleton linker protein,to catalyze its O-GlcNAcylation.Our data further show that Ezrin OGlcNAcylation promotes its localization to the cell cortex,thereby stimulating the membrane-cytoskeleton interaction needed for efficient phagocytosis.These findings identify a previously unrecognized role for protein O-GlcNAcylation in phagocytosis with important implications in both health and diseases.

关键词： O-GlcNAcylation Phagocytosis Retinal pigment epithelium Ezrin cytoskeleton

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