近端小管中的脂肪分解刺激脂蛋白受体、BMP-SMAD 信号传导与肾脏疾病

IF 10.3 1区 医学 Q1 UROLOGY & NEPHROLOGY Journal of The American Society of Nephrology Pub Date : 2024-08-01 Epub Date: 2024-05-29 DOI:10.1681/ASN.0000000000000382
Min Jiang, Xiangdong Wang, Zhenni Chen, Xin Wang, Yanan An, Lixia Ding, Mengyuan Xu, Baozhen Fan, Peng Jiao, Chao Wang, Mingxia Wang, Hui Sun, Shengtian Zhao, Yongfeng Gong
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引用次数: 0

摘要

背景:溶脂刺激脂蛋白受体(LSR)是一种单通道膜蛋白,在上皮细胞和内皮细胞的三细胞紧密连接组织中发挥重要作用,但其在肾脏生理和疾病发展中的功能仍不清楚:方法:产生条件性Lsr缺失小鼠,并对其进行分析,以研究LSR在近端肾小管中的功能。以单侧缺血再灌注为损伤模型,研究LSR在急性肾损伤(AKI)和慢性肾病(CKD)进展中的作用。采用全转录组RNA测序、免疫荧光、双荧光素酶报告基因检测、共免疫沉淀、RNA免疫沉淀以及腺相关病毒介导的基因过表达和敲除等方法进行了详细的机理分析:结果:在肾脏中发现了 LSR 的核定位。结果:LSR在肾脏中的核定位被发现。近端肾小管特异性Lsr基因敲除小鼠在单侧缺血再灌注损伤中的肾损伤和纤维化程度比野生型小鼠轻。LSR缺失导致Chrdl1下调和近端小管BMP-SMAD信号激活。用 CHRDL1 治疗可抵消 LSR 缺失对单侧缺血损伤肾脏的保护作用。此外,全身给药 Chrdl1 shRNA 可减轻损伤诱导的肾脏纤维化。LSR与近端肾小管细胞核中的14-3-3θ形成复合物,从而减少了人类抗原R与14-3-3θ之间的相互作用,进而导致未结合的人类抗原R转位到细胞质中。缺乏 LSR 会促进 14-3-3θ 与人类抗原 R 的结合,从而可能导致细胞质中人类抗原 R 水平的降低。人类抗原R水平的降低损害了Chrdl1 mRNA的稳定性,随后导致BMP-SMAD信号的激活:结论:在近端肾小管中缺失 LSR 会降低 Chrdl1 对 BMP-SMAD 信号的激活作用,从而改善肾脏疾病。
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Lipolysis-Stimulated Lipoprotein Receptor in Proximal Tubule, BMP-SMAD Signaling, and Kidney Disease.
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来源期刊
Journal of The American Society of Nephrology
Journal of The American Society of Nephrology 医学-泌尿学与肾脏学
CiteScore
22.40
自引率
2.90%
发文量
492
审稿时长
3-8 weeks
期刊介绍: The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews. Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication. JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.
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