Circulating Extracellular RNA Markers of Liver Regeneration

Irene K. Yan, Xue Wang, Yan Asmann, Hiroaki Haga, Tushar C Patel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background and Aims Although a key determinant of hepatic recovery after injury is active liver regeneration, the ability to detect ongoing regeneration is lacking. The restoration of liver mass after hepatectomy involves systemic changes with coordinated changes in gene expression guiding regenerative responses, activation of progenitor cells, and proliferation of quiescent hepatocytes. We postulated that these responses involve intercellular communication involving extracellular RNA and that these could represent biomarkers of active regenerative responses. Methods RNA sequencing was performed to identify temporal changes in serum extracellular noncoding RNA after partial hepatectomy in C57BL/6 male mice. Tissue expression of selected RNA was performed by microarray analysis and validated using qRT-PCR. Digital PCR was used to detect and quantify serum expression of selected RNA. Results A peak increase in extracellular RNA content occurred six hours after hepatectomy. RNA sequencing identified alterations in several small non-coding RNA including known and novel microRNAs, snoRNAs, tRNA, antisense and repeat elements after partial hepatectomy. Combinatorial effects and network analyses identified signal regulation, protein complex assembly, and signal transduction as the most common biological processes targeted by miRNA that altered. miR-1A and miR-181 were most significantly altered microRNA in both serum and in hepatic tissues, and their presence in serum was quantitated using digital PCR. Conclusions Extracellular RNA selectively enriched during acute regeneration can be detected within serum and represent biomarkers of ongoing liver regeneration in mice. The ability to detect ongoing active regeneration would improve the assessment of hepatic recovery from liver injury.

Original languageEnglish (US)
Article numbere0155888
JournalPLoS One
Volume11
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

liver regeneration
Liver Regeneration
Liver
Hepatectomy
RNA
liver
MicroRNAs
microRNA
RNA Sequence Analysis
Regeneration
Serum
Polymerase Chain Reaction
biomarkers
sequence analysis
Biomarkers
Small Nucleolar RNA
Biological Phenomena
Small Untranslated RNA
cell communication
Untranslated RNA

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Circulating Extracellular RNA Markers of Liver Regeneration. / Yan, Irene K.; Wang, Xue; Asmann, Yan; Haga, Hiroaki; Patel, Tushar C.

In: PLoS One, Vol. 11, No. 7, e0155888, 01.07.2016.

Research output: Contribution to journalArticle

Yan, Irene K. ; Wang, Xue ; Asmann, Yan ; Haga, Hiroaki ; Patel, Tushar C. / Circulating Extracellular RNA Markers of Liver Regeneration. In: PLoS One. 2016 ; Vol. 11, No. 7.
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