Michal Mrug, Elias Mrug, Frida Rosenblum, Jiandong Chen, Xiangqin Cui, Anupam Agarwal, Abolfazl Zarjou
{"title":"急性肾损伤期间不同物种巨噬细胞不同的发育重编程足迹","authors":"Michal Mrug, Elias Mrug, Frida Rosenblum, Jiandong Chen, Xiangqin Cui, Anupam Agarwal, Abolfazl Zarjou","doi":"10.1152/ajprenal.00013.2024","DOIUrl":null,"url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a common finding in hospitalized patients, particularly those who are critically ill. The development of AKI is associated with several adverse outcomes including mortality, morbidity, progression to chronic kidney disease, and an increase in healthcare expenditure. Despite the well-established negative impact of AKI and rigorous efforts to better define, identify, and implement targeted therapies, the overall approach to the treatment of AKI continues to principally encompass supportive measures. This enduring challenge is primarily due to the heterogeneous nature of insults that activate many independent and overlapping molecular pathways. Consequently, it is evident that the identification of common mechanisms that mediate the pathogenesis of AKI, independent of etiology and engaged pathophysiological pathways, is of paramount importance and could lead to the identification of novel therapeutic targets. To better distinguish the commonly modulated mechanisms of AKI, we explored the transcriptional characteristics of human kidney biopsies from patients with acute tubular necrosis (ATN), and acute interstitial nephritis (AIN) using a NanoString inflammation panel. Subsequently, we used publicly available single-cell transcriptional resources to better interpret the generated transcriptional findings. Our findings identify robust acute kidney injury (AKI-induced) developmental reprogramming of macrophages (MΦ) with the expansion of <i>C1Q</i><sup>+</sup>, <i>CD163</i><sup>+</sup> MΦ that is independent of the etiology of AKI and conserved across mouse and human species. These results would expand the current understanding of the pathophysiology of AKI and potentially offer novel targets for additional studies to enhance the translational transition of AKI research.<b>NEW & NOTEWORTHY</b> Our findings identify robust acute kidney injury (AKI)-induced developmental reprogramming of macrophages (MΦ) with the expansion of <i>C1Q</i><sup>+</sup>, <i>CD163</i><sup>+</sup> MΦ that is independent of the etiology of AKI and conserved across mouse and human species.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208015/pdf/","citationCount":"0","resultStr":"{\"title\":\"Distinct developmental reprogramming footprint of macrophages during acute kidney injury across species.\",\"authors\":\"Michal Mrug, Elias Mrug, Frida Rosenblum, Jiandong Chen, Xiangqin Cui, Anupam Agarwal, Abolfazl Zarjou\",\"doi\":\"10.1152/ajprenal.00013.2024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Acute kidney injury (AKI) is a common finding in hospitalized patients, particularly those who are critically ill. The development of AKI is associated with several adverse outcomes including mortality, morbidity, progression to chronic kidney disease, and an increase in healthcare expenditure. Despite the well-established negative impact of AKI and rigorous efforts to better define, identify, and implement targeted therapies, the overall approach to the treatment of AKI continues to principally encompass supportive measures. This enduring challenge is primarily due to the heterogeneous nature of insults that activate many independent and overlapping molecular pathways. Consequently, it is evident that the identification of common mechanisms that mediate the pathogenesis of AKI, independent of etiology and engaged pathophysiological pathways, is of paramount importance and could lead to the identification of novel therapeutic targets. To better distinguish the commonly modulated mechanisms of AKI, we explored the transcriptional characteristics of human kidney biopsies from patients with acute tubular necrosis (ATN), and acute interstitial nephritis (AIN) using a NanoString inflammation panel. Subsequently, we used publicly available single-cell transcriptional resources to better interpret the generated transcriptional findings. Our findings identify robust acute kidney injury (AKI-induced) developmental reprogramming of macrophages (MΦ) with the expansion of <i>C1Q</i><sup>+</sup>, <i>CD163</i><sup>+</sup> MΦ that is independent of the etiology of AKI and conserved across mouse and human species. These results would expand the current understanding of the pathophysiology of AKI and potentially offer novel targets for additional studies to enhance the translational transition of AKI research.<b>NEW & NOTEWORTHY</b> Our findings identify robust acute kidney injury (AKI)-induced developmental reprogramming of macrophages (MΦ) with the expansion of <i>C1Q</i><sup>+</sup>, <i>CD163</i><sup>+</sup> MΦ that is independent of the etiology of AKI and conserved across mouse and human species.</p>\",\"PeriodicalId\":93867,\"journal\":{\"name\":\"American journal of physiology. Renal physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208015/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of physiology. Renal physiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1152/ajprenal.00013.2024\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Renal physiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1152/ajprenal.00013.2024","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/15 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
急性肾损伤(AKI)是住院病人,尤其是危重病人的常见病。急性肾损伤的发生与多种不良后果相关,包括死亡率、发病率、慢性肾脏病的进展以及医疗费用的增加。尽管 AKI 的负面影响已得到充分证实,而且人们也在为更好地定义、识别和实施靶向疗法而不懈努力,但治疗 AKI 的总体方法仍以支持性措施为主。这一长期存在的挑战主要是由于损伤的异质性激活了许多独立和重叠的分子通路。因此,识别介导 AKI 发病机制的共同机制(与病因和参与的病理生理途径无关)显然至关重要,并可帮助识别新的治疗靶点。为了更好地区分 AKI 的常见调控机制,我们使用 NanoString 炎症面板探索了急性肾小管坏死(ATN)和急性间质性肾炎(AIN)患者肾活检组织的转录特征。随后,我们利用公开的单细胞转录资源更好地解释了所生成的转录结果。我们的研究结果表明,AKI诱导的巨噬细胞(MΦ)发育重编程与C1Q+、CD163+ MΦ的扩增无关,而且在小鼠和人类物种中是一致的。这些结果将扩展目前对 AKI 病理生理学的理解,并有可能为更多研究提供新的目标,从而加强 AKI 研究的转化过渡。
Distinct developmental reprogramming footprint of macrophages during acute kidney injury across species.
Acute kidney injury (AKI) is a common finding in hospitalized patients, particularly those who are critically ill. The development of AKI is associated with several adverse outcomes including mortality, morbidity, progression to chronic kidney disease, and an increase in healthcare expenditure. Despite the well-established negative impact of AKI and rigorous efforts to better define, identify, and implement targeted therapies, the overall approach to the treatment of AKI continues to principally encompass supportive measures. This enduring challenge is primarily due to the heterogeneous nature of insults that activate many independent and overlapping molecular pathways. Consequently, it is evident that the identification of common mechanisms that mediate the pathogenesis of AKI, independent of etiology and engaged pathophysiological pathways, is of paramount importance and could lead to the identification of novel therapeutic targets. To better distinguish the commonly modulated mechanisms of AKI, we explored the transcriptional characteristics of human kidney biopsies from patients with acute tubular necrosis (ATN), and acute interstitial nephritis (AIN) using a NanoString inflammation panel. Subsequently, we used publicly available single-cell transcriptional resources to better interpret the generated transcriptional findings. Our findings identify robust acute kidney injury (AKI-induced) developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species. These results would expand the current understanding of the pathophysiology of AKI and potentially offer novel targets for additional studies to enhance the translational transition of AKI research.NEW & NOTEWORTHY Our findings identify robust acute kidney injury (AKI)-induced developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species.