Humphreys Benjamin D
St. Louis, MO.
Trans Am Clin Climatol Assoc. 2025;135:383-392.
Outcomes after acute kidney injury (AKI) cover a wide spectrum ranging from full recovery to incomplete repair leading to transition to chronic kidney disease (CKD). This "AKI to CKD transition" is incompletely understood at a cellular level and there is a pressing need to identify the basic mechanisms of successful recovery from AKI and to develop therapeutic interventions to prevent the AKI to CKD transition. In recent years, single-cell transcriptomic and epigenomic technologies have substantially improved our understanding of cell types and states in homeostasis and after injury. In this paper, I will review our recent work applying single-cell technologies to better understand AKI and its transition to CKD, focusing on a proximal tubule cell state that we have termed "failed repair." Failed repair proximal tubule cells are characterized by pro-inflammatory and pro-fibrotic gene expression patterns and may drive the AKI to CKD transition.
急性肾损伤(AKI)后的转归范围广泛,从完全恢复到不完全修复,进而发展为慢性肾脏病(CKD)。这种“AKI向CKD的转变”在细胞水平上尚未完全明晰,迫切需要明确AKI成功恢复的基本机制,并开发预防AKI向CKD转变的治疗干预措施。近年来,单细胞转录组学和表观基因组学技术极大地增进了我们对稳态和损伤后细胞类型及状态的理解。在本文中,我将回顾我们近期应用单细胞技术来更好地理解AKI及其向CKD转变的工作,重点关注我们称之为“修复失败”的近端小管细胞状态。修复失败的近端小管细胞具有促炎和促纤维化基因表达模式,可能推动AKI向CKD的转变。