急性腎損傷（acute kidney injury, AKI）是一種常見且潛在致命的臨床症候群，其後續可能導致不完全的腎小管修復，加劇進展為慢性腎臟病（chronic kidney disease, CKD），並造成全球的高發病率和高死亡率。在AKI後的修復過程中，腎臟內會於急性期出現一群增生細胞，然而目前尚未有系統性的研究解析腎臟中增生細胞組成與時空分布特徵。此外，近年研究指出IL-33的受體ST2表現於多種免疫細胞族群，而第二型先天性淋巴細胞（ILC2）與M2巨噬細胞在腎臟修復中扮演重要角色。過去我們實驗室的研究中亦發現IL-33對於心臟纖維化有保護作用，且通過流式細胞分析後也發現ILC2及巨噬細胞為主要的擴增細胞群。而IL-33作為其主要活化因子，其對於腎臟增生細胞族群的調控機制仍待釐清。本研究以葉酸誘導急性腎損傷（FA-AKI）作為急性腎損傷小鼠模型，並透過BrdU標記追蹤增生細胞。後續結合H&E及Picro-sirius red染色評估組織病理學及纖維化進程。另外以免疫組織染色與定量分析，解析腎臟修復過程中的細胞增生特徵。我們進一步施予重組IL-33（recombinant IL-33）進行治療，探討其是否能促進腎臟組織再生，並透免疫螢光染色分析增生細胞種類，評估IL-33的腎臟保護作用。實驗結果顯示，IL-33治療可顯著提升腎臟功能恢復，減少腎小管損傷，同時也發現IL-33治療則顯著降低全體增生細胞的數量，而其中近端腎小管及間質細胞則為主要的增生細胞，並且也是在IL-33治療後顯著降低的兩種主要細胞族群。本研究揭示IL-33於急性腎損傷後調控腎臟細胞修復及降低腎臟損傷之潛力，並提供一套系統性策略用以解析FA-AKI修復過程中增生細胞的動態分布，有助於發展未來針對腎臟再生的治療策略。

Acute kidney injury (AKI) is a prevalent and clinically significant condition associated with high morbidity and mortality worldwide. A major concern in AKI is the risk of incomplete tubular repair, which can drive the transition to chronic kidney disease (CKD). In the early phase of injury, the kidney responds with a marked increase in proliferating cells, yet the cellular composition and temporal dynamics of these proliferative populations remain only partially understood. Recent studies have identified the IL-33 receptor ST2 on certain immune cell subsets, including type 2 innate lymphoid cells (ILC2s), which are known to play key roles in tissue repair. Our previous study also demonstrated that IL-33 exerts a protective role against cardiac fibrosis, with flow cytometric analysis identifying ILC2s and macrophages as the primary cell populations expanded upon IL-33 stimulation. However, how IL-33 regulates renal proliferative responses remains poorly understood. In this study, we utilized a folic acid–induced acute kidney injury (FA-AKI) mouse model to explore the role of IL-33 in renal repair. Proliferating cells were tracked using BrdU incorporation, and immunofluorescence staining combined with quantitative analysis was used to characterize proliferative profiles during the recovery phase. Recombinant IL-33 was administered therapeutically to evaluate its regenerative capacity and its impact on the composition of proliferating cells. Our results showed that IL-33 treatment significantly improved renal function recovery and attenuated tubular injury. Interestingly, IL-33 also led to a marked reduction in the total number of proliferating cells. Among these, proximal tubular epithelial cells and interstitial cells were identified as the two major proliferative populations most affected by IL-33 administration. In conclusion, this study highlights the role of IL-33 in modulating renal cell proliferation and mitigating fibrosis following AKI. It also provides a systematic approach to profiling proliferative cell populations during FA-AKI recovery, offering insights for the development for future regenerative strategies targeting kidney repair.

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