HIF-1α 激活的 IL-22/IL-22R1/Bmi1 信号在急性心肌缺血中调节心脏干细胞自我更新的作用

IF 4.5 3区 医学 Q2 CELL & TISSUE ENGINEERING
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
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引用次数: 0

摘要

急性心肌梗死(AMI)后,组织再生受损会对左心室(LV)功能和重塑产生负面影响。人们对急性心肌梗死后缺血诱导的内源性心脏干细胞(eCSCs)自我更新分裂的内在调节机制知之甚少。白细胞介素22(IL-22)/IL-22受体1(IL-22R1)途径已成为多个细胞过程的重要调节机制,包括干细胞的自我更新和增殖。然而,缺氧环境是否能通过激活IL-22/IL-22R1触发电子干细胞的自我更新仍是未知数。在本研究中,IL-22R1的上调是由于缺氧和缺血条件下缺氧诱导因子-1α(HIF-1α)的激活。全身给予 IL-22 不仅能减轻心脏重塑和炎症反应,还能促进急性心肌梗死后 eCSC 介导的心脏修复。无偏见的 RNA 微阵列分析表明,下游介质 Bmi1 可调控 CSCs 的活化。因此,HIF-1α诱导的IL-22/IL-22R1/Bmi1级联反应可以调节体外和体内电子干细胞的增殖和活化。总之,研究HIF-1α激活的IL-22/IL-22R1/Bmi1信号通路可能为通过eCSC诱导的心脏修复治疗AMI提供一种新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Role of HIF-1α-Activated IL-22/IL-22R1/Bmi1 Signaling Modulates the Self-Renewal of Cardiac Stem Cells in Acute Myocardial Ischemia

Role of HIF-1α-Activated IL-22/IL-22R1/Bmi1 Signaling Modulates the Self-Renewal of Cardiac Stem Cells in Acute Myocardial Ischemia

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.

Graphical Abstract

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来源期刊
Stem Cell Reviews and Reports
Stem Cell Reviews and Reports 医学-细胞生物学
CiteScore
9.30
自引率
4.20%
发文量
0
审稿时长
3 months
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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