{"title":"通过激活Nrf2和α2-肾上腺素能受体信号通路促进小鼠肠道干细胞干性的改良系统。","authors":"Xingyu Zhou, Li Yang, Sentao Song, Xiaolei Yin","doi":"10.3724/abbs.2025078","DOIUrl":null,"url":null,"abstract":"<p><p>Intestinal stem cells (ISCs) maintain epithelial homeostasis through continuous self-renewal and differentiation, but their regulatory mechanisms remain incompletely understood. Using a simplified culture system, we identify two novel pathways that synergistically enhance stem cell characteristics: antioxidant signaling through 2-phospho-L-ascorbic acid (pVc) and α2-adrenergic receptor (α2-AR) activation by dexmedetomidine (Dex). Mechanistic studies reveal that pVc promotes stem cell maintenance through Nrf2-mediated antioxidant responses, while α2-AR activation functions through suppression of cAMP signaling. <i>In vivo</i> administration of these compounds enhances intestinal epithelial renewal while maintaining proper stem cell positioning and identity. Notably, α2-AR activation promotes regeneration after radiation injury by enhancing proliferation of stem cells produced by Bmi1 <sup>+</sup> cells in the post-injury process, demonstrating therapeutic potential. These findings advance our understanding of ISC regulation and suggest new strategies for protecting intestinal integrity during injury or disease.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A modified system to promote stemness of mouse intestinal stem cells by activating Nrf2 and α2-adrenergic receptor signaling pathway.\",\"authors\":\"Xingyu Zhou, Li Yang, Sentao Song, Xiaolei Yin\",\"doi\":\"10.3724/abbs.2025078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Intestinal stem cells (ISCs) maintain epithelial homeostasis through continuous self-renewal and differentiation, but their regulatory mechanisms remain incompletely understood. Using a simplified culture system, we identify two novel pathways that synergistically enhance stem cell characteristics: antioxidant signaling through 2-phospho-L-ascorbic acid (pVc) and α2-adrenergic receptor (α2-AR) activation by dexmedetomidine (Dex). Mechanistic studies reveal that pVc promotes stem cell maintenance through Nrf2-mediated antioxidant responses, while α2-AR activation functions through suppression of cAMP signaling. <i>In vivo</i> administration of these compounds enhances intestinal epithelial renewal while maintaining proper stem cell positioning and identity. Notably, α2-AR activation promotes regeneration after radiation injury by enhancing proliferation of stem cells produced by Bmi1 <sup>+</sup> cells in the post-injury process, demonstrating therapeutic potential. These findings advance our understanding of ISC regulation and suggest new strategies for protecting intestinal integrity during injury or disease.</p>\",\"PeriodicalId\":6978,\"journal\":{\"name\":\"Acta biochimica et biophysica Sinica\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-05-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta biochimica et biophysica Sinica\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3724/abbs.2025078\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta biochimica et biophysica Sinica","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3724/abbs.2025078","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
肠干细胞(ISCs)通过持续的自我更新和分化维持上皮稳态,但其调控机制尚不完全清楚。通过简化的培养系统,我们确定了两种协同增强干细胞特征的新途径:通过2-磷酸- l -抗坏血酸(pVc)传递抗氧化信号和右美托咪定(Dex)激活α2-肾上腺素能受体(α2-AR)。机制研究表明,pVc通过nrf2介导的抗氧化反应促进干细胞维持,而α2-AR激活通过抑制cAMP信号传导发挥作用。在体内施用这些化合物可促进肠上皮细胞的更新,同时维持适当的干细胞定位和身份。值得注意的是,α2-AR激活通过增强损伤后Bmi1 +细胞产生的干细胞的增殖来促进辐射损伤后的再生,显示出治疗潜力。这些发现促进了我们对ISC调控的理解,并提出了在损伤或疾病期间保护肠道完整性的新策略。
A modified system to promote stemness of mouse intestinal stem cells by activating Nrf2 and α2-adrenergic receptor signaling pathway.
Intestinal stem cells (ISCs) maintain epithelial homeostasis through continuous self-renewal and differentiation, but their regulatory mechanisms remain incompletely understood. Using a simplified culture system, we identify two novel pathways that synergistically enhance stem cell characteristics: antioxidant signaling through 2-phospho-L-ascorbic acid (pVc) and α2-adrenergic receptor (α2-AR) activation by dexmedetomidine (Dex). Mechanistic studies reveal that pVc promotes stem cell maintenance through Nrf2-mediated antioxidant responses, while α2-AR activation functions through suppression of cAMP signaling. In vivo administration of these compounds enhances intestinal epithelial renewal while maintaining proper stem cell positioning and identity. Notably, α2-AR activation promotes regeneration after radiation injury by enhancing proliferation of stem cells produced by Bmi1 + cells in the post-injury process, demonstrating therapeutic potential. These findings advance our understanding of ISC regulation and suggest new strategies for protecting intestinal integrity during injury or disease.
期刊介绍:
Acta Biochimica et Biophysica Sinica (ABBS) is an internationally peer-reviewed journal sponsored by the Shanghai Institute of Biochemistry and Cell Biology (CAS). ABBS aims to publish original research articles and review articles in diverse fields of biochemical research including Protein Science, Nucleic Acids, Molecular Biology, Cell Biology, Biophysics, Immunology, and Signal Transduction, etc.