Circulating extracellular RNA markers of liver regeneration

ABSTRACT: Background and Aims: Although the liver can regenerate after sustaining injury, the tools to detect ongoing regeneration are lacking. The restoration of the liver after hepatectomy involves rapid, sequential, and coordinated changes in gene expression that result in systemic and local changes, such as the activation of progenitor cell populations and proliferation of quiescent hepatocytes. We postulated that changes in gene expression and regenerative programs could be activated within target cells through the transfer of extracellular RNA across cells or within the circulation, coordinating tissue response, and these extracellular RNA could represent biomarkers of the hepatic regenerative response. Methods: We identified temporal changes in circulating extracellular RNA at selected time periods up to 24 hours after partial hepatectomy in mice. (CD-1 males) Results: A peak increase in extracellular RNA content occurred 6 hours after hepatectomy. RNA sequencing was performed to identify the circulating extracellular non-coding RNA released after partial hepatectomy. To identify candidate markers, we used bioinformatics analyses to find the enriched RNA in the circulation after hepatectomy. We then performed tissue expression analysis for selected non-coding RNA and correlated it to these findings. Finally, a digital PCR assay was used to detect and quantify the expression of selected extracellular RNA in serum samples. Conclusions: Extracellular RNA that were selectively enriched during acute regeneration were detected within the circulation and represent biomarkers of ongoing liver regeneration in mice. The ability to detect ongoing active regeneration would benefit the evaluation of hepatic recovery after liver injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE77045 | GEO | 2019/01/20

REPOSITORIES: GEO