Chromatin accessibility dynamics dictate renal tubular epithelial cell response to injury

Xinyi Cao, Jiuchen Wang, Tianye Zhang, Zhiheng Liu, Lijun Liu, Ying Chen, Zehua Li, Youlu Zhao, Qi Yu, Tong Liu, Jing Nie, Yuanjie Niu, Yupeng Chen (), Li Yang () and Lirong Zhang ()
Additional contact information
Xinyi Cao: Tianjin Medical University
Jiuchen Wang: Tianjin Medical University
Tianye Zhang: Tianjin Medical University
Zhiheng Liu: Tianjin Medical University
Lijun Liu: Peking University First Hospital; Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment (Peking University), Ministry of Education of China
Ying Chen: Peking University First Hospital; Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment (Peking University), Ministry of Education of China
Zehua Li: Peking University First Hospital; Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment (Peking University), Ministry of Education of China
Youlu Zhao: Peking University First Hospital; Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment (Peking University), Ministry of Education of China
Qi Yu: Peking University First Hospital; Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment (Peking University), Ministry of Education of China
Tong Liu: The Second Hospital of Tianjin Medical University
Jing Nie: Southern Medical University
Yuanjie Niu: The Second Hospital of Tianjin Medical University, Tianjin Medical University
Yupeng Chen: Tianjin Medical University
Li Yang: Peking University First Hospital; Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment (Peking University), Ministry of Education of China
Lirong Zhang: Tianjin Medical University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Renal tubular epithelial cells (TECs) can initiate an adaptive response to completely recover from mild acute kidney injury (AKI), whereas severe injury often leads to persistence of maladaptive repair and progression to kidney fibrosis. Through profiling of active DNA regulatory elements by ATAC-seq, we reveal widespread, dynamic changes in the chromatin accessibility of TECs after ischemia–reperfusion injury. We show that injury-specific domains of regulatory chromatin become accessible prior to gene activation, creating poised chromatin states to activate the consequent gene expression program and injury response. We further identify RXRα as a key transcription factor in promoting adaptive repair. Activation of RXRα by bexarotene, an FDA-approved RXRα agonist, restores the chromatin state and gene expression program to protect TECs against severe kidney injury. Together, our findings elucidate a chromatin-mediated mechanism underlying differential responses of TECs to varying injuries and identify RXRα as a therapeutic target of acute kidney injury.

Date: 2022
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34854-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34854-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34854-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().