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

• Published in: Stem cell reviews and reports
• Main Authors: Lee, Wei, Lin, Syuan-Ling, Chiang, Chih-Sheng, Chen, Jui-Yu, Chieng, Wee-Wei, Huang, Shu-Rou, Chang, Ting-Yu, Linju Yen, B, Hung, Mien-Chie, Chang, Kuan-Cheng, Lee, Hsu-Tung, Jeng, Long-Bin, Shyu, Woei-Cherng
• Format: Journal Article
• Language: English
• Published: United States 12.09.2024
• Subjects: Hypoxia inducible factor 1α (HIF-1α); Interleukin 22 (IL-22)/IL-22 receptor 1 (IL-22R1); Endogenous cardiac stem cells (eCSCs); Acute myocardial infarction (AMI); Bmi1
• ISSN: 2629-3269; 2629-3277; 2629-3277
• DOI: 10.1007/s12015-024-10774-8

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.