The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps
Surgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was...
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| creator | Yoshimoto, Koichi Ikeguchi, Ryosuke Noguchi, Takashi Ando, Maki Sakamoto, Daichi Iwai, Terunobu Nishitani, Kohei Ikeda, Hanako Ohashi Kakizuka, Akira Matsuda, Shuichi |
| description | Surgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was to evaluate the effect of KUS121, a VCP modulator, on flap ischemia using a rodent model. 26 Sprague-Dawley rats were randomly divided into two groups. The experimental group was intraperitoneally administered with 100 mg/kg KUS121 dissolved in 5% glucose solution 1 hour before surgery and once per day after surgery. The control group received the same amount of glucose solution on the same schedule. On day 7, 33.6 ± 3.7% of skin flaps in the control group had developed black necrosis compared with 26.4 ± 3.6% in the KUS121 group (p < 0.01). Immunohistochemistry showed that the KUS121 treatment reduced the number of apoptotic cells in the distal third of the flap (p < 0.01); moreover, in the KUS121-treated rats, the number of cells expressing CHOP, an endoplasmic reticulum (ER) stress marker, in the middle third of the flap was significantly lower than in the controls (p < 0.01). We examined the mRNA expression of Ddit3 (CHOP) and Casp3 (caspase-3) on day one after the surgery; mRNA expression of both genes appeared to decrease in the KUS121 group, as compared with the control group, although differences between groups were not significant. Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap. |
| doi_str_mv | 10.1371/journal.pone.0299882 |
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However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was to evaluate the effect of KUS121, a VCP modulator, on flap ischemia using a rodent model. 26 Sprague-Dawley rats were randomly divided into two groups. The experimental group was intraperitoneally administered with 100 mg/kg KUS121 dissolved in 5% glucose solution 1 hour before surgery and once per day after surgery. The control group received the same amount of glucose solution on the same schedule. On day 7, 33.6 ± 3.7% of skin flaps in the control group had developed black necrosis compared with 26.4 ± 3.6% in the KUS121 group (p < 0.01). Immunohistochemistry showed that the KUS121 treatment reduced the number of apoptotic cells in the distal third of the flap (p < 0.01); moreover, in the KUS121-treated rats, the number of cells expressing CHOP, an endoplasmic reticulum (ER) stress marker, in the middle third of the flap was significantly lower than in the controls (p < 0.01). We examined the mRNA expression of Ddit3 (CHOP) and Casp3 (caspase-3) on day one after the surgery; mRNA expression of both genes appeared to decrease in the KUS121 group, as compared with the control group, although differences between groups were not significant. Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0299882</identifier><identifier>PMID: 39724048</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies ; Apoptosis ; Apoptosis - drug effects ; Biology and Life Sciences ; Caspase 3 - genetics ; Caspase 3 - metabolism ; Caspase-3 ; Complications ; Complications and side effects ; Damage patterns ; Dosage and administration ; Drug development ; Endoplasmic reticulum ; Endoplasmic Reticulum Stress - drug effects ; Enzyme inhibitors ; Flaps (Surgery) ; Gene expression ; Glucose ; Immunohistochemistry ; Injuries ; Injury prevention ; Ischemia ; Ischemia - drug therapy ; Laboratories ; Male ; Medicine and Health Sciences ; Necrosis ; Plastic surgery ; Postoperative ; Prevention ; Proteins ; Rats ; Rats, Sprague-Dawley ; Reconstructive surgery ; Risk factors ; Skin ; Skin & tissue grafts ; Skin injuries ; Soft tissues ; Surgery ; Surgical Flaps ; Testing ; Transcription Factor CHOP - genetics ; Transcription Factor CHOP - metabolism ; Valosin Containing Protein - genetics ; Valosin Containing Protein - metabolism</subject><ispartof>PloS one, 2024-12, Vol.19 (12), p.e0299882</ispartof><rights>Copyright: © 2024 Yoshimoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Yoshimoto 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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Yoshimoto et al 2024 Yoshimoto et al</rights><rights>2024 Yoshimoto 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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c465t-5eef05f335778104721dd4b33e042095e218b2ed84b6a38cc25d171661f022193</cites><orcidid>0000-0003-0802-1255 ; 0000-0003-4525-7849 ; 0009-0004-2397-2766</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671021/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671021/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39724048$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoshimoto, Koichi</creatorcontrib><creatorcontrib>Ikeguchi, Ryosuke</creatorcontrib><creatorcontrib>Noguchi, Takashi</creatorcontrib><creatorcontrib>Ando, Maki</creatorcontrib><creatorcontrib>Sakamoto, Daichi</creatorcontrib><creatorcontrib>Iwai, Terunobu</creatorcontrib><creatorcontrib>Nishitani, Kohei</creatorcontrib><creatorcontrib>Ikeda, Hanako Ohashi</creatorcontrib><creatorcontrib>Kakizuka, Akira</creatorcontrib><creatorcontrib>Matsuda, Shuichi</creatorcontrib><title>The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Surgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was to evaluate the effect of KUS121, a VCP modulator, on flap ischemia using a rodent model. 26 Sprague-Dawley rats were randomly divided into two groups. The experimental group was intraperitoneally administered with 100 mg/kg KUS121 dissolved in 5% glucose solution 1 hour before surgery and once per day after surgery. The control group received the same amount of glucose solution on the same schedule. On day 7, 33.6 ± 3.7% of skin flaps in the control group had developed black necrosis compared with 26.4 ± 3.6% in the KUS121 group (p < 0.01). 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Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biology and Life Sciences</subject><subject>Caspase 3 - genetics</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase-3</subject><subject>Complications</subject><subject>Complications and side effects</subject><subject>Damage patterns</subject><subject>Dosage and administration</subject><subject>Drug development</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum Stress - drug effects</subject><subject>Enzyme inhibitors</subject><subject>Flaps (Surgery)</subject><subject>Gene expression</subject><subject>Glucose</subject><subject>Immunohistochemistry</subject><subject>Injuries</subject><subject>Injury prevention</subject><subject>Ischemia</subject><subject>Ischemia - 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However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was to evaluate the effect of KUS121, a VCP modulator, on flap ischemia using a rodent model. 26 Sprague-Dawley rats were randomly divided into two groups. The experimental group was intraperitoneally administered with 100 mg/kg KUS121 dissolved in 5% glucose solution 1 hour before surgery and once per day after surgery. The control group received the same amount of glucose solution on the same schedule. On day 7, 33.6 ± 3.7% of skin flaps in the control group had developed black necrosis compared with 26.4 ± 3.6% in the KUS121 group (p < 0.01). Immunohistochemistry showed that the KUS121 treatment reduced the number of apoptotic cells in the distal third of the flap (p < 0.01); moreover, in the KUS121-treated rats, the number of cells expressing CHOP, an endoplasmic reticulum (ER) stress marker, in the middle third of the flap was significantly lower than in the controls (p < 0.01). We examined the mRNA expression of Ddit3 (CHOP) and Casp3 (caspase-3) on day one after the surgery; mRNA expression of both genes appeared to decrease in the KUS121 group, as compared with the control group, although differences between groups were not significant. Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39724048</pmid><doi>10.1371/journal.pone.0299882</doi><orcidid>https://orcid.org/0000-0003-0802-1255</orcidid><orcidid>https://orcid.org/0000-0003-4525-7849</orcidid><orcidid>https://orcid.org/0009-0004-2397-2766</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_3149480006 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Antibodies Apoptosis Apoptosis - drug effects Biology and Life Sciences Caspase 3 - genetics Caspase 3 - metabolism Caspase-3 Complications Complications and side effects Damage patterns Dosage and administration Drug development Endoplasmic reticulum Endoplasmic Reticulum Stress - drug effects Enzyme inhibitors Flaps (Surgery) Gene expression Glucose Immunohistochemistry Injuries Injury prevention Ischemia Ischemia - drug therapy Laboratories Male Medicine and Health Sciences Necrosis Plastic surgery Postoperative Prevention Proteins Rats Rats, Sprague-Dawley Reconstructive surgery Risk factors Skin Skin & tissue grafts Skin injuries Soft tissues Surgery Surgical Flaps Testing Transcription Factor CHOP - genetics Transcription Factor CHOP - metabolism Valosin Containing Protein - genetics Valosin Containing Protein - metabolism |
| title | The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T23%3A19%3A00IST&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=The%20effect%20of%20KUS121,%20a%20novel%20VCP%20modulator,%20against%20ischemic%20injury%20in%20random%20pattern%20flaps&rft.jtitle=PloS%20one&rft.au=Yoshimoto,%20Koichi&rft.date=2024-12-26&rft.volume=19&rft.issue=12&rft.spage=e0299882&rft.pages=e0299882-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0299882&rft_dat=%3Cgale_plos_%3EA821383087%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=3149480006&rft_id=info:pmid/39724048&rft_galeid=A821383087&rft_doaj_id=oai_doaj_org_article_30accd22951e4b6d97afe20933e62b42&rfr_iscdi=true |