Chronological Profiling of Plasma Native Peptides after Hepatectomy in Pigs: Toward the Discovery of Human Biomarkers for Liver Regeneration
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...
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| Veröffentlicht in: | PloS one 2017-01, Vol.12 (1), p.e0167647-e0167647 |
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| creator | 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 |
| description | 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_str_mv | 10.1371/journal.pone.0167647 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0167647</identifier><identifier>PMID: 28060824</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Beads ; Biology and life sciences ; Biomarkers ; Care and treatment ; Cascades ; Chromatography, High Pressure Liquid ; Clinical trials ; Computer and Information Sciences ; Diagnostic systems ; Feasibility studies ; Female ; Fragmentation ; Fragments ; Gastrointestinal surgery ; Gene expression ; Hemoglobin ; Hepatectomy ; Histones ; Hogs ; Humans ; Liver ; Liver diseases ; Liver Regeneration ; Livestock ; Medical research ; Medicine ; Medicine and Health Sciences ; Peptides ; Peptides - blood ; Physiological aspects ; Plasma ; Proteins ; Regeneration ; Regeneration (Biology) ; ROC Curve ; Rodents ; Science ; Signaling ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Surgical outcomes ; Swine ; Tandem Mass Spectrometry</subject><ispartof>PloS one, 2017-01, Vol.12 (1), p.e0167647-e0167647</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Iguchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>Animals</subject><subject>Beads</subject><subject>Biology and life sciences</subject><subject>Biomarkers</subject><subject>Care and treatment</subject><subject>Cascades</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Clinical trials</subject><subject>Computer and Information Sciences</subject><subject>Diagnostic systems</subject><subject>Feasibility studies</subject><subject>Female</subject><subject>Fragmentation</subject><subject>Fragments</subject><subject>Gastrointestinal surgery</subject><subject>Gene expression</subject><subject>Hemoglobin</subject><subject>Hepatectomy</subject><subject>Histones</subject><subject>Hogs</subject><subject>Humans</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Liver 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Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iguchi, Kohta</au><au>Hatano, Etsuro</au><au>Nirasawa, Takashi</au><au>Iwasaki, Noriyuki</au><au>Sato, Motohiko</au><au>Yamamoto, Gen</au><au>Yamanaka, Kenya</au><au>Okamoto, Tatsuya</au><au>Kasai, Yosuke</au><au>Nakamura, Naohiko</au><au>Fuji, Hiroaki</au><au>Sakai, Tomohito</au><au>Kakuda, Nobuto</au><au>Seo, Satoru</au><au>Taura, Kojiro</au><au>Tashiro, Kei</au><au>Uemoto, Shinji</au><au>Ikegawa, Masaya</au><au>Kanungo, Jyotshna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronological Profiling of Plasma Native Peptides after Hepatectomy in Pigs: Toward the Discovery of Human Biomarkers for Liver Regeneration</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-01-06</date><risdate>2017</risdate><volume>12</volume><issue>1</issue><spage>e0167647</spage><epage>e0167647</epage><pages>e0167647-e0167647</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28060824</pmid><doi>10.1371/journal.pone.0167647</doi><tpages>e0167647</tpages><orcidid>https://orcid.org/0000-0001-8731-9919</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-01, Vol.12 (1), p.e0167647-e0167647 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1856128601 |
| source | Open Access: PubMed Central; MEDLINE; Public Library of Science (PLoS) Journals Open Access; DOAJ Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Animals Beads Biology and life sciences Biomarkers Care and treatment Cascades Chromatography, High Pressure Liquid Clinical trials Computer and Information Sciences Diagnostic systems Feasibility studies Female Fragmentation Fragments Gastrointestinal surgery Gene expression Hemoglobin Hepatectomy Histones Hogs Humans Liver Liver diseases Liver Regeneration Livestock Medical research Medicine Medicine and Health Sciences Peptides Peptides - blood Physiological aspects Plasma Proteins Regeneration Regeneration (Biology) ROC Curve Rodents Science Signaling Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Surgical outcomes Swine Tandem Mass Spectrometry |
| title | Chronological Profiling of Plasma Native Peptides after Hepatectomy in Pigs: Toward the Discovery of Human Biomarkers for Liver Regeneration |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T18%3A32%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chronological%20Profiling%20of%20Plasma%20Native%20Peptides%20after%20Hepatectomy%20in%20Pigs:%20Toward%20the%20Discovery%20of%20Human%20Biomarkers%20for%20Liver%20Regeneration&rft.jtitle=PloS%20one&rft.au=Iguchi,%20Kohta&rft.date=2017-01-06&rft.volume=12&rft.issue=1&rft.spage=e0167647&rft.epage=e0167647&rft.pages=e0167647-e0167647&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0167647&rft_dat=%3Cgale_plos_%3EA476711047%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1856128601&rft_id=info:pmid/28060824&rft_galeid=A476711047&rft_doaj_id=oai_doaj_org_article_38fa4ee2483b45b08a5658356c986b82&rfr_iscdi=true |