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CD9 role in proliferation, rejuvenation, and therapeutic applications

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Genes & Diseases 2024年第3期11卷 95-97页

作者： Sai Priyanka Kodam Neda Baghban Mujib Ullah Institutefor Immunityand Transplantation Stem Cell Biology and Regenerative MedicineSchool of MedicineMolecular Medicine Department of MedicineStanford UniversityPaloAltoCA94304USA

The CD9 gene,also known as the Tspan29 gene,codes for a protein called CD9,which is a member of the tetraspanin family of transmembrane proteins.^(1) The CD9 protein is involved in various cellular processes,including cell proliferation,differentiation,adhesion,and migration.^(1,2) CD9 has also been found to play a role in the regulation of stem cell proliferation and differentiation.

关键词： migration. therapeutic CD9

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of Developmental biology Department of Biology University of Patras Laboratory of Cellular and molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson’s disease substantia

SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National Translational Science Center for molecular medicine & department of Cell biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome

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Journal of Pharmaceutical Analysis 2024年第1期14卷 152-155页

作者： Shuyu Zheng Yanlin Xin Jiamin Lin Zejuan Xie Keyu Cheng Shanshan Wang Wenli Lu Hao Yang Tianming Lu Jun Li Ruogu Qi Yuanyuan Guo department of Biochemistry and molecular biology School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing210023China department of Neurosurgery The Second Affiliated HospitalZhejiang UniversityHangzhou310009China

The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].

关键词： NSCLC eIF4E treatment

WNT/β-catenin signaling in hepatocellular carcinoma:The aberrant activation,pathogenic roles,and therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 727-746页

作者： Anna Gajos-Michniewicz Malgorzata Czyz department of molecular biology of Cancer Medical University of LodzLodz 92-215Poland

Hepatocellular carcinoma(HCC)is a liver cancer,highly heterogeneous both at the histopathological and molecular levels.It arises from hepatocytes as the result of the accumulation of numerous genomic alterations in various signaling pathways,including canonical WNT/β-catenin,AKT/mTOR,MAPK pathways as well as signaling associated with telomere maintenance,p53/cell cycle regulation,epigenetic modifiers,and oxidative stress.The role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established,whereas in development and progression of HCC is extensively studied.Herein,we review recent advances in our understanding of how WNT/β-catenin signaling facilitates the HCC development,acquisition of stemness features,metastasis,and resistance to treatment.We outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in HCC.We discuss the pivotal roles of CTNNB1 mutations,aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.

关键词： Cancer stem cells CTNNB1 mutations Liver cancer Non-coding RNA Tumor heterogeneity

OsPDR20 is an ABCG metal transporter regulating cadmium accumulation in rice

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Journal of Environmental Sciences 2024年第2期136卷 21-34页

作者： He Li Chao Li Di Sun Zhi Min Yang department of Biochemistry and molecular biology College of Life SciencesNanjing Agricultural UniversityNanjing 210095China

Cadmium(Cd)is a non-essential toxic heavy metal,seriously posing high environmental risks to human health.Digging genetic resources relevant to functional genes is important for understanding the metal absorption and accumulation in crops and bioremediation of Cd-polluted environments.This study investigated a functionally uncharacterized ATP binding cassette transporter G family(ABCG)gene encoding a Pleiotropic Drug Resistance 20(PDR20)type metal transporter which is localized to the plasma membrane of rice.OsPDR20 was transcriptionally expressed in almost all tissues and organs in lifespan and was strongly induced in roots and shoots of young rice under Cd stress.Ectopic expression of OsPDR20 in a yeast mutant ycf1 sensitive to Cd conferred cellular tolerance with less Cd accumulation.Knockdown of OsPDR20 by RNA interference(RNAi)moderately attenuated root/shoot elongation and biomass,with reduced chlorophylls in rice grown under hydroponic medium with 2 and 10μmol/L Cd,but led to more Cd accumulation.A field trial of rice grown in a realistic Cd-contaminated soil(0.40 mg/kg)showed that RNAi plants growth and development were also compromised compared to wild-type(WT),with smaller panicles and lower spikelet fertility but little effect on yield of grains.However,OsPDR20 suppression resulted in unexpectedly higher levels of Cd accumulation in rice straw including lower leaves and culm and grain.These results suggest that OsPDR20 is actively involved in Cd accumulation and homeostasis in rice crops.The increased Cd accumulation in the RNAi plants has the potential application in phytoremediation of Cd-polluted wetland soils.

关键词： Rice ABCG transporter Cadmium accumulation Phytoremediation

维普期刊数据库

Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key Laboratory of Reproductive medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai Key Laboratory of Reproductive medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of molecular biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental stages.In a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and spermatids.To gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ cells.Despite maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)generation.In addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization experiments.To conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

Adverse effects of early-life stress:focus on the rodent neuroendocrine system

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Neural Regeneration Research 2024年第2期19卷 336-341页

作者： Seung Hyun Lee Eui-Man Jung department of molecular biology College of Natural SciencesPusan National UniversityBusanRepublic of Korea

Early-life stress is associated with a high prevalence of mental illnesses such as post-traumatic stress disorders,attention-deficit/hyperactivity disorder,schizophrenia,and anxiety or depressive behavior,which constitute major public health problems.In the early stages of brain development after birth,events such as synaptogenesis,neuron maturation,and glial differentiation occur in a highly orchestrated manner,and external stress can cause adverse long-term effects throughout life.Our body utilizes multifaceted mechanisms,including neuroendocrine and neurotransmitter signaling pathways,to appropriately process external stress.Newborn individuals first exposed to early-life stress deploy neurogenesis as a stress-defense mechanism;however,in adulthood,early-life stress induces apoptosis of mature neurons,activation of immune responses,and reduction of neurotrophic factors,leading to anxiety,depression,and cognitive and memory dysfunction.This process involves the hypothalamus-pituitary-adrenal axis and neurotransmitters secreted by the central nervous system,including norepinephrine,dopamine,and serotonin.The rodent early-life stress model is generally used to experimentally assess the effects of stress during neurodevelopment.This paper reviews the use of the early-life stress model and stress response mechanisms of the body and discusses the experimental results regarding how early-life stress mediates stress-related pathways at a high vulnerability of psychiatric disorder in adulthood.

关键词： early-life stress hypothalamic-pituitary-adrenergic axis maternal separation mental illness neurodevelopmental disorder neuroendocrine system neurotransmitter

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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