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 language | English (US) |
|---|---|
| Pages (from-to) | 134-143 |
| Number of pages | 10 |
| Journal | Journal of Surgical Research |
| Volume | 236 |
| DOIs | |
| State | Published - Apr 1 2019 |
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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 journal › Review article
}
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.
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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 -