Molecular Mechanisms and Potential Therapeutic Targets in Incisional Hernia

Finosh G. Thankam, Gunasekar Palanikumar, Robert Joseph Fitzgibbons, Devendra K. Agrawal

Research output: Contribution to journalReview article

Abstract

The pathophysiology underlying the formation, progression, and surgical healing of incisional hernia (IH) that develops as a major complication associated with abdominal laparotomy is poorly understood. The proposed mechanisms include the switch of collagen phenotype and the proliferation of abnormal fibroblasts after surgery. The focus of this article was to critically review the cellular, biochemical, and potential molecular events associated with the development of IH. The disturbance in collagen homeostasis with alterations in the expression of collagen subtypes, including type 1, type 3, type 4, and type 5, and impairment in the transdifferentiation of fibroblasts to myofibroblasts are discussed. The phenotype switch of wound-repair fibroblasts results in mechanically compromised extracellular matrix that triggers the proliferation of abnormal fibroblasts. High-mobility group box 1 could be involved in wound progression, whereas signaling events mediated by tumor necrosis factor β1, connective tissue growth factor, lysyl oxidase, and hypoxia-inducible factor 1 play significant role in the wound healing response. Thus, the ratio of tumor necrosis factorβ1: high-mobility group box 1 could be a critical determinant of the underlying pathology. Potential target sites for therapeutic intervention in the management of IH are recognized.

Original languageEnglish (US)
Pages (from-to)134-143
Number of pages10
JournalJournal of Surgical Research
Volume236
DOIs
StatePublished - Apr 1 2019

Fingerprint

Fibroblasts
Collagen
Protein-Lysine 6-Oxidase
Connective Tissue Growth Factor
Phenotype
Hypoxia-Inducible Factor 1
Myofibroblasts
Wounds and Injuries
Therapeutics
Wound Healing
Laparotomy
Extracellular Matrix
Homeostasis
Necrosis
Tumor Necrosis Factor-alpha
Pathology
Incisional Hernia
Neoplasms

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Molecular Mechanisms and Potential Therapeutic Targets in Incisional Hernia. / Thankam, Finosh G.; Palanikumar, Gunasekar; Fitzgibbons, Robert Joseph; Agrawal, Devendra K.

In: Journal of Surgical Research, Vol. 236, 01.04.2019, p. 134-143.

Research output: Contribution to journalReview article

@article{d84dd97997b64b19921342a30da78b89,
title = "Molecular Mechanisms and Potential Therapeutic Targets in Incisional Hernia",
abstract = "The pathophysiology underlying the formation, progression, and surgical healing of incisional hernia (IH) that develops as a major complication associated with abdominal laparotomy is poorly understood. The proposed mechanisms include the switch of collagen phenotype and the proliferation of abnormal fibroblasts after surgery. The focus of this article was to critically review the cellular, biochemical, and potential molecular events associated with the development of IH. The disturbance in collagen homeostasis with alterations in the expression of collagen subtypes, including type 1, type 3, type 4, and type 5, and impairment in the transdifferentiation of fibroblasts to myofibroblasts are discussed. The phenotype switch of wound-repair fibroblasts results in mechanically compromised extracellular matrix that triggers the proliferation of abnormal fibroblasts. High-mobility group box 1 could be involved in wound progression, whereas signaling events mediated by tumor necrosis factor β1, connective tissue growth factor, lysyl oxidase, and hypoxia-inducible factor 1 play significant role in the wound healing response. Thus, the ratio of tumor necrosis factorβ1: high-mobility group box 1 could be a critical determinant of the underlying pathology. Potential target sites for therapeutic intervention in the management of IH are recognized.",
author = "Thankam, {Finosh G.} and Gunasekar Palanikumar and Fitzgibbons, {Robert Joseph} and Agrawal, {Devendra K.}",
year = "2019",
month = "4",
day = "1",
doi = "10.1016/j.jss.2018.11.037",
language = "English (US)",
volume = "236",
pages = "134--143",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Molecular Mechanisms and Potential Therapeutic Targets in Incisional Hernia

AU - Thankam, Finosh G.

AU - Palanikumar, Gunasekar

AU - Fitzgibbons, Robert Joseph

AU - Agrawal, Devendra K.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - The pathophysiology underlying the formation, progression, and surgical healing of incisional hernia (IH) that develops as a major complication associated with abdominal laparotomy is poorly understood. The proposed mechanisms include the switch of collagen phenotype and the proliferation of abnormal fibroblasts after surgery. The focus of this article was to critically review the cellular, biochemical, and potential molecular events associated with the development of IH. The disturbance in collagen homeostasis with alterations in the expression of collagen subtypes, including type 1, type 3, type 4, and type 5, and impairment in the transdifferentiation of fibroblasts to myofibroblasts are discussed. The phenotype switch of wound-repair fibroblasts results in mechanically compromised extracellular matrix that triggers the proliferation of abnormal fibroblasts. High-mobility group box 1 could be involved in wound progression, whereas signaling events mediated by tumor necrosis factor β1, connective tissue growth factor, lysyl oxidase, and hypoxia-inducible factor 1 play significant role in the wound healing response. Thus, the ratio of tumor necrosis factorβ1: high-mobility group box 1 could be a critical determinant of the underlying pathology. Potential target sites for therapeutic intervention in the management of IH are recognized.

AB - The pathophysiology underlying the formation, progression, and surgical healing of incisional hernia (IH) that develops as a major complication associated with abdominal laparotomy is poorly understood. The proposed mechanisms include the switch of collagen phenotype and the proliferation of abnormal fibroblasts after surgery. The focus of this article was to critically review the cellular, biochemical, and potential molecular events associated with the development of IH. The disturbance in collagen homeostasis with alterations in the expression of collagen subtypes, including type 1, type 3, type 4, and type 5, and impairment in the transdifferentiation of fibroblasts to myofibroblasts are discussed. The phenotype switch of wound-repair fibroblasts results in mechanically compromised extracellular matrix that triggers the proliferation of abnormal fibroblasts. High-mobility group box 1 could be involved in wound progression, whereas signaling events mediated by tumor necrosis factor β1, connective tissue growth factor, lysyl oxidase, and hypoxia-inducible factor 1 play significant role in the wound healing response. Thus, the ratio of tumor necrosis factorβ1: high-mobility group box 1 could be a critical determinant of the underlying pathology. Potential target sites for therapeutic intervention in the management of IH are recognized.

UR - http://www.scopus.com/inward/record.url?scp=85058363571&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058363571&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2018.11.037

DO - 10.1016/j.jss.2018.11.037

M3 - Review article

C2 - 30694748

AN - SCOPUS:85058363571

VL - 236

SP - 134

EP - 143

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

ER -