Bone marrow stromal cell antigen-1 deficiency protects from acute kidney injury.
Bone marrow stromal cell antigen-1 deficiency protects from acute kidney injury.
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骨髓基质细胞抗原 1 缺乏症可预防急性肾损伤。
DOI：
10.1152/ajprenal.00175.2023
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Okusa,MarkD
中科院分区：
文献类型：
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作者：
Inoue,Tsuyoshi;Umene,Ryusuke;Sung,Sun-SangJ;Tanaka,Shinji;Huang,Liping;Yao,Junlan;Hashimoto,Noritatsu;Wu,Chia-Hsien;Nakamura,Yasuna;Nishino,Tomoya;Ye,Hong;Rosin,DianeL;Ishihara,Katsuhiko;Okusa,MarkD
本研究旨在探讨骨髓基质细胞抗原-1(Bst1，又称CD157)在急性肾损伤(AKI)中的作用。Bst1是一种细胞表面分子，具有多种酶活性和下游的细胞内信号通路，调节免疫反应。之前的研究已经将Bst1与卵巢癌、帕金森氏症和类风湿性关节炎等疾病联系起来。我们使用双侧缺血再灌注损伤(IRI)作为AKI模型，并建立了骨髓嵌合小鼠，以评估Bst1在骨髓源性细胞中的作用。我们还用流式细胞术检测了Bst1/CD157在造血细胞中的表达，并评价了肾脏的免疫细胞动力学。结果表明，Bst1基因缺陷(Bst1−/−)小鼠对双侧肾缺血再灌注损伤有保护作用。骨髓嵌合体实验表明，Bst1在造血细胞上的表达，而不是在实质细胞上的表达，可以诱导肾脏IRI。脾、骨髓流式细胞仪检测发现Bst1主要分布在B细胞和中性粒细胞中。在体外，Bst1−/−小鼠的中性粒细胞迁移受到抑制，而过继转移野生型Bst1+/+小鼠的中性粒细胞则取消了Bst1基因敲除小鼠的肾脏保护作用。总之，本研究表明Bst1−/−小鼠对肾缺血再灌注损伤具有保护作用，并且Bst1在中性粒细胞中的表达在诱导肾缺血再灌注损伤中起着关键作用。这些发现表明，在中性粒细胞中靶向Bst1可能是AKI的一种潜在治疗策略。NEW和NOTEWORTHY急性肾损伤(AKI)是一种严重的疾病，目前还没有得到联邦药物管理局批准的有效治疗方法，它与高死亡率有关。骨髓基质细胞抗原-1(Bst1)是一种细胞表面分子，可导致肾脏纤维化，但其在AKI中的作用尚不清楚。我们的研究表明，Bst1−/−小鼠对双侧肾缺血再灌注损伤具有保护作用。过继转移研究证实，Bst1在造血细胞中的表达，尤其是中性粒细胞，有助于肾脏双侧IRI。
This study aimed to investigate the role of bone marrow stromal cell antigen-1 (Bst1; also known as CD157) in acute kidney injury (AKI). Bst1 is a cell surface molecule with various enzymatic activities and downstream intracellular signaling pathways that modulate the immune response. Previous research has linked Bst1 to diseases such as ovarian cancer, Parkinson’s disease, and rheumatoid arthritis. We used bilateral ischemia-reperfusion injury (IRI) as an AKI model and created bone marrow chimeric mice to evaluate the role of Bst1 in bone marrow-derived cells. We also used flow cytometry to identify Bst1/CD157 expression in hematopoietic cells and evaluate immune cell dynamics in the kidney. The findings showed that Bst1-deficient (Bst1−/−) mice were protected against renal bilateral IRI. Bone marrow chimera experiments revealed that Bst1 expression on hematopoietic cells, but not parenchymal cells, induced renal IRI. Bst1 was mainly found in B cells and neutrophils by flow cytometry of the spleen and bone marrow. In vitro, migration of neutrophils fromBst1−/−mice was suppressed, and adoptive transfer of neutrophils from wild-typeBst1+/+mice abolished the renal protective effect inBst1knockout mice. In conclusion, the study demonstrated thatBst1−/−mice are protected against renal IRI and that Bst1 expression in neutrophils plays a crucial role in inducing renal IRI. These findings suggest that targeting Bst1 in neutrophils could be a potential therapeutic strategy for AKI.NEW & NOTEWORTHYAcute kidney injury (AKI), a serious disease for which there is no effective Federal Drug Administration-approved treatment, is associated with high mortality rates. Bone marrow stromal cell antigen-1 (Bst1) is a cell surface molecule that can cause kidney fibrosis, but its role in AKI is largely unknown. Our study showed thatBst1−/−mice revealed a protective effect against renal bilateral ischemia-reperfusion injury (IRI). Adoptive transfer studies confirmed that Bst1 expression in hematopoietic cells, especially neutrophils, contributed to renal bilateral IRI.