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Proc Natl Acad Sci U S A 2022 Aug 16;11933:e2204338119. doi: 10.1073/pnas.2204338119.
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Adrenergic receptor signaling induced by Klf15, a regulator of regeneration enhancer, promotes kidney reconstruction.

Suzuki N , Kanai A , Suzuki Y , Ogino H , Ochi H .

Despite the recent discovery of tissue regeneration enhancers in highly regenerative animals, upstream and downstream genetic programs connected by these enhancers still remain unclear. Here, we performed a genome-wide analysis of enhancers and associated genes in regenerating nephric tubules of Xenopus laevis. Putative enhancers were identified using assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) analyses. Their target genes were predicted based on their proximity to enhancers on genomic DNA and consistency of their transcriptome profiles to ATAC-seq/ChIP-seq profiles of the enhancers. Motif enrichment analysis identified the central role of Krüppel-like factors (Klf) in the enhancer. Klf15, a member of the Klf family, directly binds enhancers and stimulates expression of regenerative genes, including adrenoreceptor alpha 1A (adra1a), whereas inhibition of Klf15 activity results in failure of nephric tubule regeneration. Moreover, pharmacological inhibition of Adra1a-signaling suppresses nephric tubule regeneration, while its activation promotes nephric tubule regeneration and restores organ size. These results indicate that Klf15-dependent adrenergic receptor signaling through regeneration enhancers plays a central role in the genetic network for kidney regeneration.

PubMed ID: 35939709
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: adra1a cecr2 des.1 des.2 dusp6 fut4 hsp70 klf15 klf4 klf5 klf6 lhx1 pax8 rab6b sp1 sp4 tmtc2
GO keywords: kidney development [+]

Disease Ontology terms: kidney disease

Article Images: [+] show captions
References [+] :
Blackburn, Modeling congenital kidney diseases in Xenopus laevis. 2019, Pubmed, Xenbase