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Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model

Postoperative pain and delayed healing in surgical wounds, which require complex management strategies have understudied complicated mechanisms. Here we investigated temporal changes in behavior, tissue structure, and transcriptomic profiles in a rat model of a surgical incision, using hyperalgesic...

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Autores principales: Goto, Taichi, Sapio, Matthew R., Maric, Dragan, Robinson, Jeffrey M., Domenichiello, Anthony F., Saligan, Leorey N., Mannes, Andrew J., Iadarola, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293146/
https://www.ncbi.nlm.nih.gov/pubmed/34499774
http://dx.doi.org/10.1096/fj.202100347R
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author Goto, Taichi
Sapio, Matthew R.
Maric, Dragan
Robinson, Jeffrey M.
Domenichiello, Anthony F.
Saligan, Leorey N.
Mannes, Andrew J.
Iadarola, Michael J.
author_facet Goto, Taichi
Sapio, Matthew R.
Maric, Dragan
Robinson, Jeffrey M.
Domenichiello, Anthony F.
Saligan, Leorey N.
Mannes, Andrew J.
Iadarola, Michael J.
author_sort Goto, Taichi
collection PubMed
description Postoperative pain and delayed healing in surgical wounds, which require complex management strategies have understudied complicated mechanisms. Here we investigated temporal changes in behavior, tissue structure, and transcriptomic profiles in a rat model of a surgical incision, using hyperalgesic behavioral tests, histological analyses, and next‐generation RNA sequencing, respectively. The most rapidly (1 hour) expressed genes were the chemokines, Cxcl1 and Cxcl2. Consequently, infiltrating leukocytes were abundantly observed starting at 6 and peaking at 24 hours after incising which was supported by histological analysis and appearance of the neutrophil markers, S100a8 and S100a9. At this time, hyperalgesia was at a peak and overall transcriptional activity was most highly activated. At the 1‐day timepoint, Nppb, coding for natriuretic peptide precursor B, was the most strongly upregulated gene and was localized by in situ hybridization to the epidermal keratinocytes at the margins of the incision. Nppb was basically unaffected in a peripheral inflammation model transcriptomic dataset. At the late phase of wound healing, five secreted, incision‐specific peptidases, Mmp2, Aebp1, Mmp23, Adamts7, and Adamtsl1, showed increased expression, supporting the idea of a sustained tissue remodeling process. Transcripts that are specifically upregulated at each timepoint in the incision model may be potential candidates for either biomarkers or therapeutic targets for wound pain and wound healing. This study incorporates the examination of longitudinal temporal molecular responses, corresponding anatomical localization, and hyperalgesic behavioral alterations in the surgical incision model that together provide important and novel foundational knowledge to understand mechanisms of wound pain and wound healing.
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spelling pubmed-92931462022-07-20 Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model Goto, Taichi Sapio, Matthew R. Maric, Dragan Robinson, Jeffrey M. Domenichiello, Anthony F. Saligan, Leorey N. Mannes, Andrew J. Iadarola, Michael J. FASEB J Research Articles Postoperative pain and delayed healing in surgical wounds, which require complex management strategies have understudied complicated mechanisms. Here we investigated temporal changes in behavior, tissue structure, and transcriptomic profiles in a rat model of a surgical incision, using hyperalgesic behavioral tests, histological analyses, and next‐generation RNA sequencing, respectively. The most rapidly (1 hour) expressed genes were the chemokines, Cxcl1 and Cxcl2. Consequently, infiltrating leukocytes were abundantly observed starting at 6 and peaking at 24 hours after incising which was supported by histological analysis and appearance of the neutrophil markers, S100a8 and S100a9. At this time, hyperalgesia was at a peak and overall transcriptional activity was most highly activated. At the 1‐day timepoint, Nppb, coding for natriuretic peptide precursor B, was the most strongly upregulated gene and was localized by in situ hybridization to the epidermal keratinocytes at the margins of the incision. Nppb was basically unaffected in a peripheral inflammation model transcriptomic dataset. At the late phase of wound healing, five secreted, incision‐specific peptidases, Mmp2, Aebp1, Mmp23, Adamts7, and Adamtsl1, showed increased expression, supporting the idea of a sustained tissue remodeling process. Transcripts that are specifically upregulated at each timepoint in the incision model may be potential candidates for either biomarkers or therapeutic targets for wound pain and wound healing. This study incorporates the examination of longitudinal temporal molecular responses, corresponding anatomical localization, and hyperalgesic behavioral alterations in the surgical incision model that together provide important and novel foundational knowledge to understand mechanisms of wound pain and wound healing. John Wiley and Sons Inc. 2021-09-09 2021-10 /pmc/articles/PMC9293146/ /pubmed/34499774 http://dx.doi.org/10.1096/fj.202100347R Text en © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Goto, Taichi
Sapio, Matthew R.
Maric, Dragan
Robinson, Jeffrey M.
Domenichiello, Anthony F.
Saligan, Leorey N.
Mannes, Andrew J.
Iadarola, Michael J.
Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model
title Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model
title_full Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model
title_fullStr Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model
title_full_unstemmed Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model
title_short Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model
title_sort longitudinal peripheral tissue rna‐seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293146/
https://www.ncbi.nlm.nih.gov/pubmed/34499774
http://dx.doi.org/10.1096/fj.202100347R
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