Volume 14 Issue 2
Mar.  2023
Turn off MathJax
Article Contents
Article Navigation >  ORGAN TRANSPLANTATION  > 2023  >  14(2): 273-279
Li Wanli, Zhang Yingying, Zhang Ting, et al. Analysis of key genes and targeted protection methods affecting the survival of human islets[J]. ORGAN TRANSPLANTATION, 2023, 14(2): 273-279. doi: 10.3969/j.issn.1674-7445.2023.02.014
Citation: Li Wanli, Zhang Yingying, Zhang Ting, et al. Analysis of key genes and targeted protection methods affecting the survival of human islets[J]. ORGAN TRANSPLANTATION, 2023, 14(2): 273-279. doi: 10.3969/j.issn.1674-7445.2023.02.014
shu

Analysis of key genes and targeted protection methods affecting the survival of human islets

doi: 10.3969/j.issn.1674-7445.2023.02.014

  • Guangxi University of Chinese Medicine, Nanning 530001, China

More Information
  • Corresponding author: Gao Hongjun, Email: gao4056@163.com
  • Received Date: 2022-11-25
    Available Online: 2023-03-15
  • Publish Date: 2023-03-15
    Abstract
  •   Objective  To identify the key genes and targeted protection methods affecting the survival of human islets.  Methods  Using bioinformatics method, the gene expression profile (GSE53454) was selected through screening and comparison from Gene Expression Omnibus(GEO) database. GEO2R tool was employed to screen the differentially expressed gene(DEG) between the human islets exposed (exposure group) and non-exposed (non-exposure group) to interleukin (IL)-1β and interferon (IFN)-γ for 24, 48 and 72 h, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape apps.  Results  A total of 69 up-regulated DEGs and 2 down-regulated DEGs were identified. GO analysis showed that during the biological process, DEGs were enriched in the aspects of virus defense and inflammatory response. In cellular components, DEGs were significantly enriched in extracellular space, outside plasma membrane and extracellular regions. Regarding molecular functions, DEGs were significantly enriched in chemokine activity and cytokine activity. KEGG analysis revealed that DEGs were mainly enriched in multiple signaling pathways, such as cytokine-cytokine receptor interaction, virus protein-cytokine and cytokine-receptor interaction, etc. Ten key genes (STAT1, CXCL10, IRF1, IL6, CXCL9, CCL5, CXCL11, ISG15, CD274, IFIT3) with high connectivity were selected by STRING analysis, all of which were significantly up-regulated in human islets exposed to IL-1β and IFN-γ. Six genes (STAT1, CXCL10, CXCL9, CXCL11, CCL5, IL6) were screened by KEGG enrichment analysis, mainly in Toll-like receptor signaling pathway.  Conclusions  STAT1, CXCL10, CXCL9, CXCL11, CCL5 and IL6 are the key genes affecting the survival of human islets, which are mainly enriched in Toll-like receptor signaling pathway and act as important targets for islet protection.

     

    • FullText(HTML)
  • loading
    • References(42)
  • [1]
    JIANG H, LI Y, SHEN M, et al. Interferon-α promotes MHC I antigen presentation of islet β cells through STAT1-IRF7 pathway in type 1 diabetes[J]. Immunology, 2022, 166(2): 210-221. DOI: 10.1111/imm.13468.
    [2]
    周智广. B淋巴细胞亚类与自身免疫糖尿病的胰岛功能[J]. 中华医学信息导报, 2018, 33(23): 13. DOI: 10.3969/j.issn.1000-8039.2018.23.011.

    ZHOU ZG. B lymphocyte subclasses and islet function in autoimmune diabetes[J]. Chin Med News, 2018, 33(23): 13. DOI: 10.3969/j.issn.1000-8039.2018.23.011.
    [3]
    GOU W, WANG J, SONG L, et al. Alpha-1 antitrypsin suppresses macrophage activation and promotes islet graft survival after intrahepatic islet transplantation[J]. Am J Transplant, 2021, 21(5): 1713-1724. DOI: 10.1111/ajt.16342.
    [4]
    CHEN C, RONG P, YANG M, et al. The role of interleukin-1β in destruction of transplanted islets[J]. Cell Transplant, 2020, 29: 963689720934413. DOI: 10.1177/0963689720934413.
    [5]
    中华医学会器官移植学分会. 胰岛移植临床技术操作规范(2019版)[J]. 器官移植, 2019, 10(6): 621-627. DOI: 10.3969/j.issn.1674-7445.2019.06.001.

    Branch of Organ Transplantation of Chinese Medical Association. Clinical technical operation specification of pancreatic islet transplantation (2019 edition)[J]. Organ Transplant, 2019, 10(6): 621-627. DOI: 10.3969/j.issn.1674-7445.2019.06.001.
    [6]
    DUGBARTEY GJ. Carbon monoxide in pancreatic islet transplantation: a new therapeutic alternative to patients with severe type 1 diabetes mellitus[J]. Front Pharmacol, 2021, 12: 750816. DOI: 10.3389/fphar.2021.750816.
    [7]
    HUBBER EL, RACKHAM CL, JONES PM. Protecting islet functional viability using mesenchymal stromal cells[J]. Stem Cells Transl Med, 2021, 10(5): 674-680. DOI: 10.1002/sctm.20-0466.
    [8]
    YAN LL, YE LP, CHEN YH, et al. The influence of microenvironment on survival of intraportal transplanted islets[J]. Front Immunol, 2022, 13: 849580. DOI: 10.3389/fimmu.2022.849580.
    [9]
    SONG Y, FENG T, CAO W, et al. Identification of key genes in nasopharyngeal carcinoma based on bioinformatics analysis[J]. Comput Intell Neurosci, 2022: 9022700. DOI: 10.1155/2022/9022700.
    [10]
    LIU Z, OU C, XIANG S, et al. Expression and regulatory network analysis of BICC1 for aged Sca-1-positive bone narrow mesenchymal stem cells[J]. Dis Markers, 2022: 4759172. DOI: 10.1155/2022/4759172.
    [11]
    XU X, QI J, YANG J, et al. Up-regulation of TRIM32 associated with the poor prognosis of acute myeloid leukemia by integrated bioinformatics analysis with external validation[J]. Front Oncol, 2022, 12: 848395. DOI: 10.3389/fonc.2022.848395.
    [12]
    LIU C, LIU J, WU D, et al. Construction of immune-related ceRNA network in dilated cardiomyopathy: based on sex differences[J]. Front Genet, 2022, 13: 882324. DOI: 10.3389/fgene.2022.882324.
    [13]
    ZHENG H, QIAN X, TIAN W, et al. Exploration of the common gene characteristics and molecular mechanism of Parkinson's disease and Crohn's disease from transcriptome data[J]. Brain Sci, 2022, 12(6): 774. DOI: 10.3390/brainsci12060774.
    [14]
    STANLEY WJ, TRIVEDI PM, SUTHERLAND AP, et al. Differential regulation of pro-inflammatory cytokine signalling by protein tyrosine phosphatases in pancreatic β-cells[J]. J Mol Endocrinol, 2017, 59(4): 325-337. DOI: 10.1530/JME-17-0089.
    [15]
    LEBRETON F, HANNA R, WASSMER CH, et al. Mechanisms of immunomodulation and cytoprotection conferred to pancreatic islet by human amniotic epithelial cells[J]. Stem Cell Rev Rep, 2022, 18(1): 346-359. DOI: 10.1007/s12015-021-10269-w.
    [16]
    DHAYAL S, LESLIE KA, BAITY M, et al. Temporal regulation of interferon signalling in human EndoC-βH1 cells[J]. J Mol Endocrinol, 2022, 69(2): 299-313. DOI: 10.1530/JME-21-0224.
    [17]
    MOORE F, NAAMANE N, COLLI ML, et al. STAT1 is a master regulator of pancreatic β-cell apoptosis and islet inflammation[J]. J Biol Chem, 2011, 286(2): 929-941. DOI: 10.1074/jbc.M110.162131.
    [18]
    DOS SANTOS RS, MARROQUI L, VELAYOS T, et al. DEXI, a candidate gene for type 1 diabetes, modulates rat and human pancreatic beta cell inflammation via regulation of the type I IFN/STAT signalling pathway[J]. Diabetologia, 2019, 62(3): 459-472. DOI: 10.1007/s00125-018-4782-0.
    [19]
    NANO E, PETROPAVLOVSKAIA M, ROSENBERG L. Islet neogenesis associated protein (INGAP) protects pancreatic β cells from IL-1β and IFNγ-induced apoptosis[J]. Cell Death Discov, 2021, 7(1): 56. DOI: 10.1038/s41420-021-00441-z.
    [20]
    BARRA JM, KOZLOVSKAYA V, KEPPLE JD, et al. Xenotransplantation of tannic acid-encapsulated neonatal porcine islets decreases proinflammatory innate immune responses[J]. Xenotransplantation, 2021, 28(6): e12706. DOI: 10.1111/xen.12706.
    [21]
    NIGI L, BRUSCO N, GRIECO GE, et al. Pancreatic alpha-cells contribute together with beta-cells to CXCL10 expression in type 1 diabetes[J]. Front Endocrinol (Lausanne), 2020, 11: 630. DOI: 10.3389/fendo.2020.00630.
    [22]
    ZENG Z, LAN T, WEI Y, et al. CCL5/CCR5 axis in human diseases and related treatments[J]. Genes Dis, 2022, 9(1): 12-27. DOI: 10.1016/j.gendis.2021.08.004.
    [23]
    CAI XH, WANG GQ, LIANG R, et al. CORM-2 pretreatment attenuates inflammation-mediated islet dysfunction[J]. Cell Transplant, 2020, 29: 963689720903691. DOI: 10.1177/0963689720903691.
    [24]
    OH E, AHN M, AFELIK S, et al. Syntaxin 4 expression in pancreatic β-cells promotes islet function and protects functional β-cell mass[J]. Diabetes, 2018, 67(12): 2626-2639. DOI: 10.2337/db18-0259.
    [25]
    YOSHIMATSU G, KUNNATHODI F, SARAVANAN PB, et al. Pancreatic β-cell-derived IP-10/CXCL10 isletokine mediates early loss of graft function in islet cell transplantation[J]. Diabetes, 2017, 66(11): 2857-2867. DOI: 10.2337/db17-0578.
    [26]
    CHRISTEN U, KIMMEL R. Chemokines as drivers of the autoimmune destruction in type 1 diabetes: opportunity for therapeutic intervention in consideration of an optimal treatment schedule[J]. Front Endocrinol (Lausanne), 2020, 11: 591083. DOI: 10.3389/fendo.2020.591083.
    [27]
    JAVEED N, HER TK, BROWN MR, et al. Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes[J]. Cell Rep, 2021, 36(8): 109613. DOI: 10.1016/j.celrep.2021.109613.
    [28]
    NARDELLI TR, VANZELA EC, BENEDICTO KC, et al. Prolactin protects against cytokine-induced beta-cell death by NFκB and JNK inhibition[J]. J Mol Endocrinol, 2018, 61(1): 25-36. DOI: 10.1530/JME-16-0257.
    [29]
    ZAMMIT NW, SEEBERGER KL, ZAMERLI J, et al. Selection of a novel AAV2/TNFAIP3 vector for local suppression of islet xenograft inflammation[J]. Xenotransplantation, 2021, 28(3): e12669. DOI: 10.1111/xen.12669.
    [30]
    ABADPOUR S, TYRBERG B, SCHIVE SW, et al. Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function[J]. Diabetologia, 2020, 63(7): 1355-1367. DOI: 10.1007/s00125-020-05138-z.
    [31]
    SATO N, HAGA J, ANAZAWA T, et al. Ex vivo pretreatment of islets with mitomycin C: reduction in immunogenic potential of islets by suppressing secretion of multiple chemotactic factors[J]. Cell Transplant, 2017, 26(8): 1392-1404. DOI: 10.1177/0963689717721233.
    [32]
    KIM G, LEE HS, OH BJ, et al. Protective effect of a novel clinical-grade small molecule necrosis inhibitor against oxidative stress and inflammation during islet transplantation[J]. Am J Transplant, 2021, 21(4): 1440-1452. DOI: 10.1111/ajt.16323.
    [33]
    FUMAGALLI G, MONFRINI M, DONZELLI E, et al. Protective effect of human mesenchymal stem cells on the survival of pancreatic islets[J]. Int J Stem Cells, 2020, 13(1): 116-126. DOI: 10.15283/ijsc19094.
    [34]
    WANG K, LI L, JIN J, et al. Fatty acid synthase (Fasn) inhibits the expression levels of immune response genes via alteration of alternative splicing in islet cells[J]. J Diabetes Complications, 2022, 36(6): 108159. DOI: 10.1016/j.jdiacomp.2022.108159.
    [35]
    FANG C, HUANG Y, PEI Y, et al. Genome-wide gene expression profiling reveals that CD274 is up-regulated new-onset type 1 diabetes mellitus[J]. Acta Diabetol, 2017, 54(8): 757-767. DOI: 10.1007/s00592-017-1005-y.
    [36]
    CHITTEZHATH M, WAI CMM, TAY VSY, et al. TLR4 signals through islet macrophages to alter cytokine secretion during diabetes[J]. J Endocrinol, 2020, 247(1): 87. DOI: 10.1530/JOE-20-0131.
    [37]
    BENNER SE, WALTER DL, THUMA JR, et al. Toll-like receptor 3 is critical to the pancreatic islet milieu that is required for coxsackievirus B4-induced type 1 diabetes in female nonobese diabetic mice[J]. Pancreas, 2022, 51(1): 48-55. DOI: 10.1097/MPA.0000000000001960.
    [38]
    LOKA RS, SONG Z, SLETTEN ET, et al. Heparan sulfate mimicking glycopolymer prevents pancreatic β cell destruction and suppresses inflammatory cytokine expression in islets under the challenge of upregulated heparanase[J]. ACS Chem Biol, 2022, 17(6): 1387-1400. DOI: 10.1021/acschembio.1c00908.
    [39]
    WANG H, WEI J, HU H, et al. Oral administration of bacterial β cell expansion factor A (BefA) alleviates diabetes in mice with type 1 and type 2 diabetes[J]. Oxid Med Cell Longev, 2022: 9206039. DOI: 10.1155/2022/9206039.
    [40]
    KWON EY, CHOI MS. Luteolin targets the toll-like receptor signaling pathway in prevention of hepatic and adipocyte fibrosis and insulin resistance in diet-induced obese mice[J]. Nutrients, 2018, 10(10): 1415. DOI: 10.3390/nu10101415.
    [41]
    CHUNG H, HONG SJ, CHOI SW, et al. High mobility group box 1 secretion blockade results in the reduction of early pancreatic islet graft loss[J]. Biochem Biophys Res Commun, 2019, 514(4): 1081-1086. DOI: 10.1016/j.bbrc.2019.05.003.
    [42]
    ZHANG J, CHEN L, WANG F, et al. Extracellular HMGB1 exacerbates autoimmune progression and recurrence of type 1 diabetes by impairing regulatory T cell stability[J]. Diabetologia, 2020, 63(5): 987-1001. DOI: 10.1007/s00125-020-05105-8.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (259) PDF downloads(73) Cited by()
    Proportional views
    Related

    WeChat Subscription Account

    Wechat Service Account

    Contact Us
    • Tel：020-38736410
    • Email: organtranspl@163.com
    • Address：The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou
    • Editorial Office of Organ Transplantation  粤ICP备2021030844号
    Links

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return