Gene regulation in regeneration after acute kidney injury.

ABSTRACT

Acute kidney injury (AKI) is a common condition associated with significant morbidity, mortality, and cost. Injured kidney tissue can regenerate after many forms of AKI. However, there are no treatments in routine clinical practice to encourage recovery. In part, this shortcoming is due to an incomplete understanding of the genetic mechanisms that orchestrate kidney recovery. The advent of high-throughput sequencing technologies and genetic mouse models has opened an unprecedented window into the transcriptional dynamics that accompany both successful and maladaptive repair. AKI recovery shares similar cell-state transformations with kidney development, which can suggest common mechanisms of gene regulation. Several powerful bioinformatic strategies have been developed to infer the activity of gene regulatory networks by combining multiple forms of sequencing data at single-cell resolution. These studies highlight not only shared stress responses but also key changes in gene regulatory networks controlling metabolism. Furthermore, chromatin immunoprecipitation studies in injured kidneys have revealed dynamic epigenetic modifications at enhancer elements near target genes. This review will highlight how these studies have enhanced our understanding of gene regulation in injury response and regeneration.