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semaphorin 7a participants in pterygium by regulating vascular endothelial growth factor

International Journal of Ophthalmology(English edition) 2019年第6期12卷 892-897页

作者： Yun-Fei Han Zhen Liu Bang Wang Wei Zhu Jing-Zhen Li Yue-Qin Qi Xiao-Jing Li Yan-Yun Xu Xiao-Xiao Dou Guo-Ying Mu Department of Ophthalmology Shandong Provincial Hospital Affiliated to Shandong UniversityJinan 250021Shandong ProvinceChina Aier Eye Hospital Group Hubin Aier Eye HospitalBinzhou 256600Shandong ProvinceChina Department of Ophthalmology the Second People’s Hospital of LiaochengLinqing 252600Shandong ProvinceChina Neonatal Intensive Care Unit Binzhou Medical University HospitalBinzhou 256600Shandong ProvinceChina Department of Ophthalmology Jinan Central Hospital Affiliated to Shandong UniversityJinan 250013Shandong ProvinceChina Department of Cardiovascular Medicine the Second Affiliated Hospital of Zhejiang University College of MedicineHangzhou 310009Zhejiang ProvinceChina

AIM: To investigate the relationship between semaphorin 7a expression and cell proliferation and migration in pterygium fibroblasts. METHODS: Twenty-six patients with surgically diagnosed pterygium were enrolled, including 15 cases of primary pterygium and 11 cases of recurrent pterygium. In addition, 12 cases of normal conjunctival tissue were collected. The expression of semaphorin 7a in normal conjunctival tissue, primary pterygium and recurrent pterygium was detected by real-time polymerase chain reaction. Recurrent pterygium fibroblasts were isolated and cultured, and the expression of semaphorin 7a was silenced by small interfering RNA(siRNA) interference technique. Furthermore, the effects of si-semaphorin 7a interference on the mRNA and protein levels of β1-integrin, vascular endothelial growth factor A(VEGFA) and vascular endothelial growth factor receptor(VEGFR), and on fibroblast proliferation were analyzed. Transwell assay was used to detect the effect of semaphorin 7a interference on fibroblast migration. RESULTS: semaphorin 7a was highly expressed in the primary pterygium and recurrent pterygium samples than that of the normal conjunctival tissue. Compared with the primary pterygium, the expression of semaphoring 7a in the recurrent pterygium samples was significantly increased(Psemaphorin 7a transfection, and as well as the cell proliferation and migration. CONCLUSION: semaphorin 7a might play important roles in the pathogenesis of pterygium by affecting the expression of β1-integrin, VEGFA and VEGFR.

关键词： semaphorin 7a pterygium β1-integrin vascular endothelial growth factor fibroblast

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semaphorin 3A-hypoxia inducible factor 1 subunit alpha co-overexpression enhances the osteogenic differentiation of induced pluripotent stem cells-derived mesenchymal stem cells in vitro

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Chinese Medical Journal 2020年第3期133卷 301-309页

作者： Jing-Yi Li Ting-Ting Wang Chong Li Zhi-Fang Wang Shan Li Li Ma Li-Li Zheng Department of Plastic Surgery Capital Medical University Affiliated Beijing Tiantan HospitalBeijing 100050China Department of Endocrinology and Metabolism The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450000China Department of Plastic Surgery China-Japan Friendship HospitalBeijing 100029China.

Background:Mesenchymal stem or stromal cells(MSCs)derived from the induced pluripotent stem cells(iPSCs)have uniform biological activity,which makes the clinical application of MSCs in bone repair possible.Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration.The aim of this work was to evaluate the effects of semaphorin 3A(Sema3A)and hypoxia inducible factor 1 subunit alpha(HIF1α)co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs.Methods:Sema3A and HIF1αwere linked together with the three(GGGGS;G,glycine;S,serine)peptide fragment,and their co-expression in iPSC-MSCs was mediated by a lentiviral vector.The fusion protein retained the immune reactivity for both Sema3A and HIF1αas determined with Western blotting.iPSC-MSCs were infected with overexpression lentivirus(oeLenti)as negative control,oeLenti-Sema3A,oeLenti-HIF1αor oeLenti-Sema3A-HIF1αlentiviruses.Results:Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs(the activity and/or expression of osteoblast markers,such as alkaline phosphatase,osteopontin,and osteocalcin,were upregulated),and suppressed cell survival.The Sema3A-HIF1αfusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival.We further seeded iPSC-MSCs modified by SemaA-HIF1αoverexpression onto hydroxyapatite(HA)scaffolds,and evaluated their growth and differentiation on this three-dimensional material.Additional data indicated that,as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes,cells cultured in HA scaffolds grew(blank vs.HA scaffolds:0.83 vs.1.39 for survival)and differentiated better(blank vs.HA scaffolds:11.29 vs.16.62 for alkaline phosphatase activity).Conclusion:Modifying iPSC-MSCs with pro-osteogenic(Sema3A)and pro-survival(HIF1α)factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.

关键词： semaphorin 3A Hypoxia inducible factor 1 subunit alpha Induced pluripotent stem cells Mesenchymal stems Cell survival Osteogenic differentiation Hydroxyapatite scaffolds

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Identification of semaphorin 5A Interacting Protein by Applying Apriori Knowledge and Peptide Complementarity Related to Protein Evolution and Structure

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Genomics, Proteomics & Bioinformatics 2008年第3期6卷 163-174页

作者： Anguraj Sadanandam Michelle L. Varney Rakesh K. Singh Department of Pathology and Microbiology University of Nebraska Medical Center

In the post-genomic era, various computational methods that predict proteinprotein interactions at the genome level are available; however, each method has its own advantages and disadvantages, resulting in false predictions. Here we developed a unique integrated approach to identify interacting partner（s） of semaphorin 5A （SEMA5A）, beginning with seven proteins sharing similar ligand interacting residues as putative binding partners. The methods include Dwyer and Root- Bernstein/Dillon theories of protein evolution, hydropathic complementarity of protein structure, pattern of protein functions among molecules, information on domain-domain interactions, co-expression of genes and protein evolution. Among the set of seven proteins selected as putative SEMA5A interacting partners, we found the functions of Plexin B3 and Neuropilin-2 to be associated with SEMA5A. We modeled the semaphorin domain structure of Plexin B3 and found that it shares similarity with SEMA5A. Moreover, a virtual expression database search and RT-PCR analysis showed co-expression of SEMA5A and Plexin B3 and these proteins were found to have co-evolved. In addition, we confirmed the interaction of SEMA5A with Plexin B3 in co-immunoprecipitation studies. Overall, these studies demonstrate that an integrated method of prediction can be used at the genome level for discovering many unknown protein binding partners with known ligand binding domains.

关键词： domain-domain interaction semaphorin plexin protein interaction prediction

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Immune plexins and semaphorins: old proteins, new immune functions

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Protein & Cell 2013年第1期4卷 17-26页

作者： Kelly Roney Eda Holl Jenny Ting University of Chapel Hill Department of Microbiology and Immunology22-004 Lineberger Comprehensive Cancer CenterCB7295Chapel HillNC 27599USA Duke University Department of SurgeryDurhamNC 27710USA

Plexins and semaphorins are a large family of proteins that are involved in cell movement and response.The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous(Nkyimbeng-Takwi and Chapoval,2011;McCormick and Leipzig,2012;Yaron and Sprinzak,2012),epithelial(Miao et al.,1999;Fujii et al.,2002),and immune systems(Takamatsu and Kumanogoh,2012)as well as diverse cell processes including angiogenesis(Serini et al.,2009;Sakurai et al.,2012),embryogenesis(Perala et al.,2012),and cancer(Potiron et al.,2009;Micucci et al.,2010).Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin do-main(Hota and Buck,2012).The plexins and sema-phorins are divided into four and eight subfamilies respectively based on their structural homology.semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intra-cellular tails.Plexins contain the semaphorin domain and long intracellular tails(Hota and Buck,2012).The majority of plexin and semaphorin research has fo-cused on the nervous system,particularly the devel-oping nervous system,where these proteins are found to mediate many common neuronal cell processes including cell movement,cytoskeletal rearrangement,and signal transduction(Choi et al.,2008;Takamatsu et al.,2010).Their roles in the immune system are the focus of this review.

关键词： plexin semaphorin immune system den-dritic cell B cell T cell

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The contribution of oligodendrocytes and oligodendrocyte progenitor cells to central nervous system repair in multiple sclerosis： perspectives for remyelination therapeutic strategies

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Neural Regeneration Research 2017年第12期12卷 1939-1944页

作者： Adriana Octaviana Dulamea Department of Neurology Fundeni Clinical Institute University of Medicine and Pharmacy "Carol Davila" Bucharest Romania

Oligodencrocytes（OLs） are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis（MS）, there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells（OPCs） and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.

关键词： multiple sclerosis oligodencrocytes oligodendrocyte progenitor cells demyelination remyelination semaphorin basic helix-loop-helix transcription factor oligodendrocyte transcription factor 2 leucin-rich repeatand immunoglobulin-like-domain-containing nogo receptor-interacting protein I canonical Notch signaling endocrine receptors

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Myelin-based inhibitors of oligodendrocyte myelination: clues from axonal growth and regeneration

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Neuroscience Bulletin 2013年第2期29卷 177-188页

作者： Feng Mei S.Y.Christin Chong Jonah R.Chan Department of Neurology Program in Neuroscience and the MS Research GroupUniversity of California

The differentiation of and myelination by oligodendrocytes （OLs） are exquisitely regulated by a series of intrinsic and extrinsic mechanisms. As each OL can make differing numbers of myelin segments with variable lengths along similar axon tracts, myelination can be viewed as a graded process shaped by inhibitory/ inductive cues during development. Myelination by OLs is a prime example of an adaptive process determined by the microenvironment and architecture of the central nervous system （CNS）. In this review, we discuss how myelin formation by OLs may be controlled by the heterogeneous microenvironment of the CNS. Then we address recent findings demonstrating that neighboring OLs may compete for available axon space, and highlight our current understanding of myelin-based inhibitors of axonal regeneration that are potentially responsible for the reciprocal dialogue between OLs and determine the numbers and lengths of myelin internodes. Understanding the mechanisms that control the spatiotemporal regulation of myelinogenic potential during development may provide valuable insight into therapeutic strategies for promoting remyelination in an inhibitory microenvironment.

关键词： differentiation myelin nogo-A LINGO-l semaphorin ephrin netrin-1

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semaphorin 3A过表达对H_2O_2诱导的人脐静脉内皮细胞损伤的影响

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中国病理生理杂志 2017年第6期33卷 1080-1085页

作者：王海芳赵向绒霍雪萍孙晶莹武翔龙牛银波胡军刘勤社陕西省人民医院中心实验室陕西西安710068 西北工业大学生命学院陕西西安710072 陕西中医药大学陕西西安712046

目的:探讨semaphorin 3A(Sema 3A)对过氧化氢(H_2O_2)诱导的人脐静脉内皮细胞(HUVECs)损伤的影响。方法:构建Sema 3A过表达载体,以脂质体转染法转染HUVECs,过表达效果以qPCR和Western blot法验证;待测细胞以200μmol/L H_2O_2处理4 h;q... 详细信息

目的:探讨semaphorin 3A(Sema 3A)对过氧化氢(H_2O_2)诱导的人脐静脉内皮细胞(HUVECs)损伤的影响。方法:构建Sema 3A过表达载体,以脂质体转染法转染HUVECs,过表达效果以qPCR和Western blot法验证;待测细胞以200μmol/L H_2O_2处理4 h;qPCR法检测炎性细胞因子水平;乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)和丙二醛(MDA)水平以相应比色法检测;细胞活力以MTT法检测;流式细胞术检测细胞凋亡,凋亡相关蛋白cleaved caspase-3及Bcl-2水平以Western blot法检测。结果:Sema 3A过表达能显著增加H_2O_2诱导的HUVECs凋亡、炎性细胞因子分泌以及LDH和MDA含量,同时显著抑制SOD活性和细胞活力;Sema 3A对未经H_2O_2处理的HUVECs没有损伤效应,即其对HUVECs的损伤具有H_2O_2依赖性。结论:Sema 3A能显著加重H_2O_2诱导的HUVECs损伤,在氧化应激所致的内皮细胞损伤过程中发挥促进作用。

关键词：动脉粥样硬化 semaphorin 3A 过氧化氢人脐静脉内皮细胞

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Regulation of immune cell responses by semaphorins and their receptors

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Cellular & Molecular Immunology 2010年第2期7卷 83-88页

作者： Hyota Takamatsu Tatsusada Okuno Atsushi Kumanogoh Department of Immunopathology Research Institute for Microbial Diseases Osaka University Suita Osaka Japan World Premier International Immunology FrontierResearch Center Osaka University Suita Osaka Japan

semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called ＇immune semaphorins＇, are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins and their receptors in immune responses： their functions in cell-cell interactions and their involvement in immune cell trafficking.

关键词： semaphorin immune regulation immune cell trafficking tumorigenesis autoimmune diseases

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semaphorin 3A对大鼠慢性心肌梗死周边区交感神经重构的影响

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武汉大学学报（医学版） 2010年第2期31卷 145-148,I0004页

作者：吴擎江洪陆志锋黎梅温华知武汉大学人民医院心血管内科湖北武汉430060

目的:探讨不同浓度semaphorin 3A(Sema 3A)对大鼠心肌梗死慢性期梗死周边区交感神经重构及心室颤动阈值(室颤阈值)的影响。方法:80只大鼠随机分为两组。心梗组(20只):结扎冠状动脉前降支;Sema 3A组(60只):结扎冠状动脉前降支后于梗死周... 详细信息

目的:探讨不同浓度semaphorin 3A(Sema 3A)对大鼠心肌梗死慢性期梗死周边区交感神经重构及心室颤动阈值(室颤阈值)的影响。方法:80只大鼠随机分为两组。心梗组(20只):结扎冠状动脉前降支;Sema 3A组(60只):结扎冠状动脉前降支后于梗死周边区分别注入不同浓度的Sema 3A。8周后测定大鼠梗死周边区室颤阈值,免疫组化染色检测生长相关蛋白43(GAP43)和酪氨酸羟化酶(TH)阳性纤维密度。结果:室颤阈值在Sema 3A注射组中随药物浓度增加而升高,1.0mg/L浓度组相比心梗组有明显提高(P<0.05)。Sema 3A注射组GAP43和TH神经纤维密度与心梗组差异明显(P<0.05);且随药物浓度提高神经纤维密度呈下降趋势,在药物浓度达到1.0mg/L时表现显著(与1.0mg/L组相比P<0.05)。结论:不同浓度的Sema 3A对室颤阈值有不同的提升效应,而对大鼠心肌梗死后交感神经重构产生不同的抑制作用。

关键词：心肌梗死 semaphorin 3A 交感神经重构

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Promotion of Sema4D expression by tumor-associated macrophages: Significance in gastric carcinoma

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World Journal of Gastroenterology 2018年第5期24卷 593-601页

作者： Han Li Jin-Shen Wang Lin-Jun Mu Ke-Shu Shan Le-Ping Li Yan-Bing Zhou Department of General Surgery Affiliated Hospital of Qingdao University Department of Gastrointestinal Surgery Shandong Provincial Hospital Affiliated to Shandong University Department of Emergency Surgery Weifang People’s Hospital

AIM To study the role of semaphorin 4 D(Sema4 D) expression promoted by tumor-associated macrophages(TAMs) in gastric carcinoma cells and its clinical significance in the invasion and metastasis of gastric carcinoma.METHODS CD68 and Sema4 D expression was analyzed in gastric carcinoma and adjacent normal tissues from 290 patients using the immunohistochemical streptavidinperoxidase method, and their relationships with clinicopathological features were evaluated. Human M2 macrophages were induced in vitro and co-cultured in non-contact with gastric carcinoma SGC-7901 cells. Changes in the secretory Sema4 D level in the SGC-7901 cell supernatant were measured using an enzymelinked immunosorbent assay. The effects of TAMs on SGC-7901 cell invasion and migration were assessed with invasion and migration assays, respectively.RESULTS CD68 and Sema4 D protein expression was significantly higher in gastric carcinoma tissues than in adjacent normal tissues(71.7% vs 33.8% and 74.5% vs 42.8%, respectively; P < 0.01). CD68 and Sema4 D protein expression was significantly associated with histological differentiation, TNM stage, and lymph node metastasis(P < 0.05), and their expression levels were positively correlated with one another(r = 0.467, P < 0.01). In the in vitro experiment, secretory Sema4 D protein expression was significantly increased in the supernatant of SGC-7901 cells co-cultured with TAMs compared with the blank control(1224.13 ± 29.43 vs 637.15 ± 33.84, P < 0.01). Cell invasion and metastasis were enhanced in the Transwell invasion and migration assays(P < 0.01).CONCLUSION TAMs promote the invasion and metastasis of gastric carcinoma cells possibly through upregulated secretory Sema4 D protein expression. Combined detection of TAM markers, CD68 and Sema4 D, in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression.

关键词： Gastric carcinoma CD68 semaphorin 4D Tumor-associated macrophages

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