Faculty Information |
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Article types | Original article |
Language | English |
Refereed paper | Not refereed |
Title | Chronological Profiling of Plasma Native Peptides after Hepatectomy in Pigs: Toward the Discovery of Human Biomarkers for Liver Regeneration |
Journal | Formal name:PloS one Abbreviation:PLoS One ISSN code:1932-6203(Electronic)1932-6203(Linking) |
Domestic / Foregin | Foregin |
Volume, Number, Page | 12(1),pp.e0167647 |
Papers・Author | Iguchi Kohta, 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 |
Publication date | 2017/01 |
Papers・Description | UNASSIGNED: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 ClinProtTM 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. |
DOI | 10.1371/journal.pone.0167647 |
PMID | 28060824 |