学術雑誌論文 Chronological Profiling of Plasma Native Peptides after Hepatectomy in Pigs: Toward the Discovery of Human Biomarkers for Liver Regeneration

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

12 ( 1 ) 2017-01-06 , Public Library of Science
ISSN:1932-6203
内容記述
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.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/218474/1/journal.pone.0167647.pdf

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