HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis.
HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis.
复制标题
HNRNPA 1介导的miR-483- 5 p从肾小管上皮细胞中分选出来促进糖尿病肾病诱导的肾间质纤维化的进展
DOI：
10.1038/s41419-021-03460-x
复制
发表时间：
2021-03-10
影响因子：
9
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Liu D;Liu F;Li Z;Pan S;Xie J;Zhao Z;Liu Z;Zhang J;Liu Z
糖尿病肾病（DN）是1型和2型糖尿病的严重并发症，肾间质纤维化在DN的进展中起关键作用。本研究旨在探讨miR-483-5p在dn诱导的肾间质纤维化中的作用及其潜在机制。在这项研究中，我们证实了miR-483-5p在1型和2型糖尿病小鼠肾组织和高糖（HG）刺激的小管上皮细胞（TECs）中的表达降低，在1型和2型糖尿病小鼠肾组织衍生的外泌体中的表达升高。miR-483-5p在体外抑制纤维化相关基因的表达，在体内抑制肾间质纤维化。在机制上，miR-483-5p结合TIMP2和MAPK1， TIMP2和MAPK1与HG条件下miR-483-5p对肾TECs的调节相结合。重要的是，hnrnpa1介导的外泌体分选将细胞内的miR-483-5p从tec转运到尿液中。我们的研究结果阐明了hnrnpa1介导的外泌体分拣将细胞内的miR-483-5p从TECs转运到尿液中，从而减轻细胞内miR-483-5p对MAPK1和TIMP2 mrna的抑制，最终促进细胞外基质沉积和dn诱导的肾间质纤维化的进展。
Diabetic nephropathy (DN) is a serious complication in type 1 and type 2 diabetes, and renal interstitial fibrosis plays a key role in DN progression. Here, we aimed to probe into the role and potential mechanism of miR-483-5p in DN-induced renal interstitial fibrosis. In this study, we corroborated that miR-483-5p expression was lessened in type 1 and type 2 diabetic mice kidney tissues and high glucose (HG)-stimulated tubular epithelial cells (TECs), and raised in the exosomes derived from renal tissues in type 1 and type 2 diabetic mice. miR-483-5p restrained the expressions of fibrosis-related genes in vitro and renal interstitial fibrosis in vivo. Mechanistically, miR-483-5p bound both TIMP2 and MAPK1, and TIMP2 and MAPK1 were bound up with the regulation of miR-483-5p on renal TECs under HG conditions. Importantly, HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine. Our results expounded that HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine, thus lessening the restraint of cellular miR-483-5p on MAPK1 and TIMP2 mRNAs, and ultimately boosting extracellular matrix deposition and the progression of DN-induced renal interstitial fibrosis.
登录
查看更多内容
狼疮性肾炎和糖尿病肾病中新型尿液 MicroRNA 生物标志物的鉴定、确认和复制。
影响因子：
9.3
作者：
Cardenas-Gonzalez M;Srivastava A;Pavkovic M;Bijol V;Rennke HG;Stillman IE;Zhang X;Parikh S;Rovin BH;Afkarian M;de Boer IH;Himmelfarb J;Waikar SS;Vaidya VS
通讯作者：
Vaidya VS
DOI：
10.3791/57718
发表时间：
2018-06-20
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Ding W;Yousefi K;Shehadeh LA
通讯作者：
Shehadeh LA
影响因子：
4.8
作者：
Hernandez-Barrantes, S;Toth, M;Fridman, R
通讯作者：
Fridman, R
影响因子：
13.6
作者：
Borges, Fernanda T.;Melo, Sonia A.;Kalluri, Raghu
通讯作者：
Kalluri, Raghu
影响因子：
4.8
作者：
Dang, Viet D.;Jella, Kishore Kumar;Alli, Abdel A.
通讯作者：
Alli, Abdel A.