Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis.

IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular biomedicine Pub Date : 2024-06-28 DOI:10.1186/s43556-024-00187-x
Shuai Guo, Yi Dong, Ran Du, Yu-Xing Liu, Shu Liu, Qin Wang, Ji-Shi Liu, Hui Xu, Yu-Jie Jiang, Huang Hao, Liang-Liang Fan, Rong Xiang
{"title":"Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis.","authors":"Shuai Guo, Yi Dong, Ran Du, Yu-Xing Liu, Shu Liu, Qin Wang, Ji-Shi Liu, Hui Xu, Yu-Jie Jiang, Huang Hao, Liang-Liang Fan, Rong Xiang","doi":"10.1186/s43556-024-00187-x","DOIUrl":null,"url":null,"abstract":"<p><p>Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211315/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular biomedicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s43556-024-00187-x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
单细胞转录组分析显示,ER 蛋白 Reticulon3 的减少推动了肾脏纤维化的进展。
慢性肾脏病(CKD)是一个严重的全球性健康难题,其产生原因复杂。尽管我们之前的研究表明,网状神经元3(RTN3)的缺乏会加速肾脏疾病的进展,但对RTN3对肾脏功能和病理影响的深入研究仍然不足。为了满足这一迫切需要,我们培育了Rtn3缺失小鼠,以研究RTN3蛋白缺乏对CKD的影响。我们对来自健康小鼠和 Rtn3 缺失小鼠肾皮质的 47,885 个细胞进行了单细胞转录组分析,比较了 14 种不同细胞类型的空间结构和表达谱。我们的分析表明,RTN3 缺乏会导致肾细胞的空间组织和基因表达谱发生显著改变,从而反映出慢性肾功能衰竭的病理变化。具体来说,RTN3 缺乏与 Lars2 过度表达有关,而 Lars2 过度表达又会导致线粒体功能障碍和活性氧水平升高。这种转变诱导肾上皮细胞从功能状态转变为纤维化状态,从而促进肾纤维化。此外,研究还发现 RTN3 缺乏会推动内皮细胞向间质转化过程,并破坏细胞间的交流,从而进一步加剧肾脏纤维化。免疫组化和Western-Blot技术被用来验证这些观察结果,从而加强了RTN3在CKD发病机制中的关键作用。CKD 中 RTN3 蛋白的缺乏会导致细胞结构和分子特征发生深刻变化。我们的工作旨在提高人们对 RTN3 在 CKD 中作用的认识,并将其定位为一种有前景的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
6.30
自引率
0.00%
发文量
0
审稿时长
10 weeks
期刊最新文献
T cell receptor repertoire characteristics and therapeutic potential of tumor infiltrating lymphocytes (TILs) derived from metastatic lymph node in cervical cancer. Decorin-armed oncolytic adenovirus promotes natural killers (NKs) activation and infiltration to enhance NK therapy in CRC model. Post-translational modifications of fibrinogen: implications for clotting, fibrin structure and degradation. Systemic lupus erythematosus: pathogenesis and targeted therapy. The functions of apolipoproteins and lipoproteins in health and disease.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1