{"title":"Role of HIF-1α-Activated IL-22/IL-22R1/Bmi1 Signaling Modulates the Self-Renewal of Cardiac Stem Cells in Acute Myocardial Ischemia","authors":"Wei Lee, Syuan-Ling Lin, Chih-Sheng Chiang, Jui-Yu Chen, Wee-Wei Chieng, Shu-Rou Huang, Ting-Yu Chang, B. Linju Yen, Mien-Chie Hung, Kuan-Cheng Chang, Hsu-Tung Lee, Long-Bin Jeng, Woei-Cherng Shyu","doi":"10.1007/s12015-024-10774-8","DOIUrl":null,"url":null,"abstract":"<p>Impaired tissue regeneration negatively impacts on left ventricular (LV) function and remodeling after acute myocardial infarction (AMI). Little is known about the intrinsic regulatory machinery of ischemia-induced endogenous cardiac stem cells (eCSCs) self-renewing divisions after AMI. The interleukin 22 (IL-22)/IL-22 receptor 1 (IL-22R1) pathway has emerged as an important regulator of several cellular processes, including the self-renewal and proliferation of stem cells. However, whether the hypoxic environment could trigger the self-renewal of eCSCs via IL-22/IL-22R1 activation remains unknown. In this study, the upregulation of IL-22R1 occurred due to activation of hypoxia-inducible factor-1α (HIF-1α) under hypoxic and ischemic conditions. Systemic IL-22 administration not only attenuated cardiac remodeling, inflammatory responses, but also promoted eCSC-mediated cardiac repair after AMI. Unbiased RNA microarray analysis showed that the downstream mediator Bmi1 regulated the activation of CSCs. Therefore, the HIF-1α-induced IL-22/IL-22R1/Bmi1 cascade can modulate the proliferation and activation of eCSCs in vitro and in vivo. Collectively, investigating the HIF-1α-activated IL-22/IL-22R1/Bmi1 signaling pathway might offer a new therapeutic strategy for AMI via eCSC-induced cardiac repair.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":"59 1","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Reviews and Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12015-024-10774-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0
Abstract
Impaired tissue regeneration negatively impacts on left ventricular (LV) function and remodeling after acute myocardial infarction (AMI). Little is known about the intrinsic regulatory machinery of ischemia-induced endogenous cardiac stem cells (eCSCs) self-renewing divisions after AMI. The interleukin 22 (IL-22)/IL-22 receptor 1 (IL-22R1) pathway has emerged as an important regulator of several cellular processes, including the self-renewal and proliferation of stem cells. However, whether the hypoxic environment could trigger the self-renewal of eCSCs via IL-22/IL-22R1 activation remains unknown. In this study, the upregulation of IL-22R1 occurred due to activation of hypoxia-inducible factor-1α (HIF-1α) under hypoxic and ischemic conditions. Systemic IL-22 administration not only attenuated cardiac remodeling, inflammatory responses, but also promoted eCSC-mediated cardiac repair after AMI. Unbiased RNA microarray analysis showed that the downstream mediator Bmi1 regulated the activation of CSCs. Therefore, the HIF-1α-induced IL-22/IL-22R1/Bmi1 cascade can modulate the proliferation and activation of eCSCs in vitro and in vivo. Collectively, investigating the HIF-1α-activated IL-22/IL-22R1/Bmi1 signaling pathway might offer a new therapeutic strategy for AMI via eCSC-induced cardiac repair.
期刊介绍：
The purpose of Stem Cell Reviews and Reports is to cover contemporary and emerging areas in stem cell research and regenerative medicine. The journal will consider for publication:
i) solicited or unsolicited reviews of topical areas of stem cell biology that highlight, critique and synthesize recent important findings in the field.
ii) full length and short reports presenting original experimental work.
iii) translational stem cell studies describing results of clinical trials using stem cells as therapeutics.
iv) papers focused on diseases of stem cells.
v) hypothesis and commentary articles as opinion-based pieces in which authors can propose a new theory, interpretation of a controversial area in stem cell biology, or a stem cell biology question or paradigm. These articles contain more speculation than reviews, but they should be based on solid rationale.
vi) protocols as peer-reviewed procedures that provide step-by-step descriptions, outlined in sufficient detail, so that both experts and novices can apply them to their own research.
vii) letters to the editor and correspondence.
In order to facilitate this exchange of scientific information and exciting novel ideas, the journal has created five thematic sections, focusing on:
i) the role of adult stem cells in tissue regeneration;
ii) progress in research on induced pluripotent stem cells, embryonic stem cells and mechanism governing embryogenesis and tissue development;
iii) the role of microenvironment and extracellular microvesicles in directing the fate of stem cells;
iv) mechanisms of stem cell trafficking, stem cell mobilization and homing with special emphasis on hematopoiesis;
v) the role of stem cells in aging processes and cancerogenesis.
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