Polynucleotide phosphorylase protects against renal tubular injury via blocking mt-dsRNA-PKR-eIF2α axis

Yujie Zhu, Mingchao Zhang, Weiran Wang, Shuang Qu, Minghui Liu, Weiwei Rong, Wenwen Yang, Hongwei Liang, Caihong Zeng, Xiaodong Zhu, Limin Li (), Zhihong Liu () and Ke Zen ()
Additional contact information
Yujie Zhu: Nanjing University School of Life Sciences
Mingchao Zhang: Nanjing University School of Life Sciences
Weiran Wang: Nanjing University School of Life Sciences
Shuang Qu: China Pharmaceutical University
Minghui Liu: China Pharmaceutical University
Weiwei Rong: Nanjing University School of Life Sciences
Wenwen Yang: Nanjing University School of Life Sciences
Hongwei Liang: China Pharmaceutical University
Caihong Zeng: Nanjing University School of Medicine
Xiaodong Zhu: Nanjing University School of Medicine
Limin Li: China Pharmaceutical University
Zhihong Liu: Nanjing University School of Medicine
Ke Zen: Nanjing University School of Life Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Renal tubular atrophy is a hallmark of chronic kidney disease. The cause of tubular atrophy, however, remains elusive. Here we report that reduction of renal tubular cell polynucleotide phosphorylase (PNPT1) causes renal tubular translation arrest and atrophy. Analysis of tubular atrophic tissues from renal dysfunction patients and male mice with ischemia-reperfusion injuries (IRI) or unilateral ureteral obstruction (UUO) treatment shows that renal tubular PNPT1 is markedly downregulated under atrophic conditions. PNPT1 reduction leads to leakage of mitochondrial double-stranded RNA (mt-dsRNA) into the cytoplasm where it activates protein kinase R (PKR), followed by phosphorylation of eukaryotic initiation factor 2α (eIF2α) and protein translational termination. Increasing renal PNPT1 expression or inhibiting PKR activity largely rescues IRI- or UUO-induced mouse renal tubular injury. Moreover, tubular-specific PNPT1-knockout mice display Fanconi syndrome-like phenotypes with impaired reabsorption and significant renal tubular injury. Our results reveal that PNPT1 protects renal tubules by blocking the mt-dsRNA-PKR-eIF2α axis.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36664-0 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:14:y:2023:i:1:d:10.1038_s41467-023-36664-0

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

DOI: 10.1038/s41467-023-36664-0

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 ().