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

• 上本, 伸二

• Hatano, Etsuro

• Nirasawa, Takashi

• Iwasaki, Noriyuki

• Sato, Motohiko

• Yamamoto, Gen

• Yamanaka, Kenya

• Okamoto, Tatsuya

• Kasai, Yosuke

• Nakamura, Naohiko

• Fuji, Hiroaki

• Sakai, Tomohito

• Kakuda, Nobuto

• Seo, Satoru

• Taura, Kojiro

• Tashiro, Kei

• Uemoto, Shinji

• Ikegawa, Masaya

抄録

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 α (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.

収録刊行物

• PLOS ONE

  PLOS ONE 12 (1), 2017-01-06

  Public Library of Science

詳細情報

• CRID: 1050282810817805824
• NII論文ID: 120005980866
• ISSN: 19326203
• HANDLE: 2433/218474
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles