論文

査読有り
2017年1月

Chronological Profiling of Plasma Native Peptides after Hepatectomy in Pigs: Toward the Discovery of Human Biomarkers for Liver Regeneration

PLOS ONE
  • Kohta Iguchi
  • Etsuro Hatano
  • Takashi Nirasawa
  • Noriyuki Iwasaki
  • Motohiko Sato
  • Gen Yamamoto
  • Kenya Yamanaka
  • Tatsuya Okamoto
  • Yosuke Kasai
  • Naohiko Nakamura
  • Hiroaki Fuji
  • Tomohito Sakai
  • Nobuto Kakuda
  • Satoru Seto
  • Kojiro Taura
  • Kei Tashiro
  • Shinji Uemoto
  • Masaya Ikegawam
  • 全て表示

12
1
開始ページ
e0167647
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0167647
出版者・発行元
PUBLIC LIBRARY SCIENCE

Liver regeneration after partial hepatectomy (PHx) is a time-dependent process, which is tightly regulated by multiple signaling cascades. Failure of this complex process leads to posthepatectomy liver failure (PHLF), which is associated with a high rate of mortality. Thus, it is extremely important to establish a useful biomarker of liver regeneration to help prevent PHLF. Here, we hypothesized that alterations in the plasma peptide profile may predict liver regeneration following PHx and hence we set up a diagnostic platform for monitoring posthepatectomy outcome. We chronologically analyzed plasma peptidomic profiles of 5 partially hepatectomized microminipigs using the ClinProt (TM) system, which consists of magnetic beads and MALDI-TOF/TOF MS. We identified endogenous circulating peptides specific to each phase of the postoperative course after PHx in pigs. Notably, peptide fragments of histones were detected immediately after PHx; the presence of these fragments may trigger liver regeneration in the very acute phase after PHx. An N-terminal fragment of hemoglobin subunit a (3627 m/z) was detected as an acute-phase-specific peptide. In the recovery phase, the short N-terminal fragments of albumin (3028, 3042 m/z) were decreased, whereas the long N-terminal fragment of the protein (8926 m/z) was increased. To further validate and extract phase-specific biomarkers using plasma peptidome after PHx, plasma specimens of 4 patients who underwent PHx were analyzed using the same method as we applied to pigs. It revealed that there was also phase-specificity in peptide profiles, one of which was represented by a fragment of complement C4b (2378 m/z). The strategy described herein is highly efficient for the identification and characterization of peptide biomarkers of liver regeneration in a swine PHx model. This strategy is feasible for application to human biomarker studies and will yield clues for understanding liver regeneration in human clinical trials.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0167647
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28060824
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000391641500013&DestApp=WOS_CPL
ID情報
  • DOI : 10.1371/journal.pone.0167647
  • ISSN : 1932-6203
  • PubMed ID : 28060824
  • Web of Science ID : WOS:000391641500013

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