JAML promotes acute kidney injury mainly through a macrophage-dependent mechanism.
JAML promotes acute kidney injury mainly through a macrophage-dependent mechanism.
复制标题
JAML 主要通过巨噬细胞依赖性机制促进急性肾损伤。
DOI：
10.1172/jci.insight.158571
复制
发表时间：
2022-06-16
期刊：
影响因子：
8
通讯作者：
Yi, Fan
中科院分区：
文献类型：
--
作者：
Huang, Wei;Wang, Bi-Ou;Hou, Yun-Feng;Fu, Yi;Cui, Si-Jia;Zhu, Jing-Han;Zhan, Xin-Yu;Li, Rong-Kun;Tang, Wei;Wu, Ji-Chao;Wang, Zi-Ying;Wang, Mei;Wang, Xiao-Jie;Zhang, Yan;Liu, Min;Xie, Yu-Sheng;Sun, Yu;Yi, Fan
尽管巨噬细胞由于其在肾脏炎症和修复中的关键作用而无疑是急性肾损伤（阿基）的有吸引力的治疗靶点，但在阿基期间巨噬细胞表型转换和巨噬细胞增多在炎症反应调节中的潜在机制仍在很大程度上不清楚。本研究阐明了连接粘附分子样蛋白（JAML）在阿基发病机制中的作用。我们发现JAML在2种不同的小鼠阿基模型中显著上调，包括肾缺血/再灌注损伤（IRI）和顺铂诱导的阿基。通过产生骨髓嵌合小鼠、巨噬细胞特异性Jaml和肾小管细胞特异性Jaml条件性敲除小鼠，我们证明JAML主要通过巨噬细胞依赖性机制促进阿基，并发现JAML介导的巨噬细胞表型极化和巨噬细胞增多是连接炎症反应与阿基的关键信号转导途径之一。从机制上讲，JAML对巨噬细胞的调节作用至少部分与巨噬细胞诱导的C型凝集素依赖性机制有关。总之，我们的研究首次探索了JAML在巨噬细胞中的新生物学功能，并得出结论，JAML是阿基的重要介质和生物标志物。药理学靶向JAML介导的信号通路在多个水平可能为阿基患者提供一种新的治疗策略。
Although macrophages are undoubtedly attractive therapeutic targets for acute kidney injury (AKI) because of their critical roles in renal inflammation and repair, the underlying mechanisms of macrophage phenotype switching and efferocytosis in the regulation of inflammatory responses during AKI are still largely unclear. The present study elucidated the role of junctional adhesion molecule–like protein (JAML) in the pathogenesis of AKI. We found that JAML was significantly upregulated in kidneys from 2 different murine AKI models including renal ischemia/reperfusion injury (IRI) and cisplatin-induced AKI. By generation of bone marrow chimeric mice, macrophage-specific and tubular cell–specific Jaml conditional knockout mice, we demonstrated JAML promoted AKI mainly via a macrophage-dependent mechanism and found that JAML-mediated macrophage phenotype polarization and efferocytosis is one of the critical signal transduction pathways linking inflammatory responses to AKI. Mechanistically, the effects of JAML on the regulation of macrophages were, at least in part, associated with a macrophage-inducible C-type lectin–dependent mechanism. Collectively, our studies explore for the first time to our knowledge new biological functions of JAML in macrophages and conclude that JAML is an important mediator and biomarker of AKI. Pharmacological targeting of JAML-mediated signaling pathways at multiple levels may provide a novel therapeutic strategy for patients with AKI.
登录
查看更多内容
影响因子：
5.5
作者：
Cao Q;Wang Y;Harris DC
通讯作者：
Harris DC
DOI：
10.1038/labinvest.2017.130
发表时间：
2018-03
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Lever JM;Yang Z;Boddu R;Adedoyin OO;Guo L;Joseph R;Traylor AM;Agarwal A;George JF
通讯作者：
George JF
影响因子：
8
作者：
Cai, Wei;Dai, Xuejiao;Chen, Jun
通讯作者：
Chen, Jun
DOI：
10.1007/s00467-017-3883-1
发表时间：
2019-04
期刊：
Pediatric nephrology (Berlin, Germany)
影响因子：
--
作者：
Han HI;Skvarca LB;Espiritu EB;Davidson AJ;Hukriede NA
通讯作者：
Hukriede NA
JAML 升高通过调节足细胞脂质代谢促进糖尿病肾病。
影响因子：
29
作者：
Fu, Yi;Sun, Yu;Yi, Fan
通讯作者：
Yi, Fan