دورية أكاديمية
HIF-1α promotes kidney organoid vascularization and applications in disease modeling.
| العنوان: | HIF-1α promotes kidney organoid vascularization and applications in disease modeling. |
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| المؤلفون: | Peng K; NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China., Xie W; NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China., Wang T; Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China., Li Y; NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China., de Dieu Habimana J; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing, 100049, China., Amissah OB; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing, 100049, China., Huang J; Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China., Chen Y; NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China., Ni B; NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China. nibin2007@163.com., Li Z; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. li_zhiyuan@gibh.ac.cn.; Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. li_zhiyuan@gibh.ac.cn.; GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China. li_zhiyuan@gibh.ac.cn.; GIBH-CUHK Joint Research Laboratory On Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Guangzhou, China. li_zhiyuan@gibh.ac.cn.; NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China. li_zhiyuan@gibh.ac.cn. |
| المصدر: | Stem cell research & therapy [Stem Cell Res Ther] 2023 Nov 19; Vol. 14 (1), pp. 336. Date of Electronic Publication: 2023 Nov 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101527581 Publication Model: Electronic Cited Medium: Internet ISSN: 1757-6512 (Electronic) Linking ISSN: 17576512 NLM ISO Abbreviation: Stem Cell Res Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central |
| مواضيع طبية MeSH: | Organoids*/blood supply , Organoids*/metabolism , Kidney*/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit*/genetics , Hypoxia-Inducible Factor 1, alpha Subunit*/metabolism , Models, Biological* , Angiogenesis*/drug effects , Angiogenesis*/physiopathology, Multipotent Stem Cells ; Humans ; Plasmids/genetics ; Gene Expression ; Stem Cells/cytology ; Stem Cells/metabolism ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Angiogenesis Inhibitors/pharmacology ; Axitinib/pharmacology ; Cells, Cultured ; Cisplatin/pharmacology ; Cell Hypoxia ; Kidney Diseases/physiopathology |
| مستخلص: | Background: Kidney organoids derived from human pluripotent stem cells (HiPSCs) hold huge applications for drug screening, disease modeling, and cell transplanting therapy. However, these applications are limited since kidney organoid cannot maintain complete morphology and function like human kidney. Kidney organoids are not well differentiated since the core of the organoid lacked oxygen, nutrition, and vasculature, which creates essential niches. Hypoxia-inducible factor-1 α (HIF-1α) serves as a critical regulator in vascularization and cell survival under hypoxia environment. Less is known about the role of HIF-1α in kidney organoids in this regard. This study tried to investigate the effect of HIF-1α in kidney organoid vascularization and related disease modeling. Methods: For the vascularization study, kidney organoids were generated from human induced pluripotent stem cells. We overexpressed HIF-1α via plasmid transfection or treated DMOG (Dimethyloxallyl Glycine, an agent for HIF-1α stabilization and accumulation) in kidney progenitor cells to detect the endothelium. For the disease modeling study, we treated kidney organoid with cisplatin under hypoxia environment, with additional HIF-1α transfection. Result: HIF-1α overexpression elicited kidney organoid vascularization. The endothelial cells and angiotool analysis parameters were increased in HIF-1α plasmid-transfected and DMOG-treated organoids. These angiogenesis processes were partially blocked by VEGFR inhibitors, semaxanib or axitinib. Cisplatin-induced kidney injury (Cleaved caspase 3) was protected by HIF-1α through the upregulation of CD31 and SOD2. Conclusion: We demonstrated that HIF-1α elicited the process of kidney organoid vascularization and protected against cisplatin-induced kidney organoid injury in hypoxia environment. (© 2023. The Author(s).) |
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| معلومات مُعتمدة: | 2022M721113 Postdoctoral Research Foundation of China; kq2208094 Changsha Science and Technology Project; 2019SK1012 Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defects in Hunan Province |
| فهرسة مساهمة: | Keywords: Cisplatin; HIF-1α; Kidney organoid; Vascularization |
| المشرفين على المادة: | 0 (HIF1A protein, human) 0 (Hypoxia-Inducible Factor 1, alpha Subunit) EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) 0 (Angiogenesis Inhibitors) 71IA9S35AJ (Semaxinib) C9LVQ0YUXG (Axitinib) Q20Q21Q62J (Cisplatin) |
| تواريخ الأحداث: | Date Created: 20231120 Date Completed: 20240201 Latest Revision: 20240201 |
| رمز التحديث: | 20240201 |
| مُعرف محوري في PubMed: | PMC10659095 |
| DOI: | 10.1186/s13287-023-03528-9 |
| PMID: | 37981699 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1757-6512 |
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| DOI: | 10.1186/s13287-023-03528-9 |