Biomarkers and heterogeneous fibroblast phenotype associated with incisional hernia

Thankam, Finosh G.; Larsen, Nicholas K.; Varghese, Ann; Bui, Thao Nguyen; Reilly, Matthew J.; Fitzgibbons, Robert J.; Agrawal, Devendra K.

doi:10.1007/s11010-021-04166-6

Cited by 13 publications

(6 citation statements)

References 35 publications

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“…Compared to the control, there were alterations in tissue architecture, fibroblast morphology, and ECM organisation in the IH tissues. These findings support the heterogeneity of the fibroblast population at the laparotomy site that could contribute to the development of IH [20].…”

Section: Aetiology and Molecular Basissupporting

confidence: 80%

Incisional Hernia: A Surgical Complication or Medical Disease?

Omar,

Zaimis,

Townsend

et al. 2023

Cureus

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Incisional hernia (IH) is a frequent complication following abdominal surgery. The development of IH could be more sophisticated than a simple anatomical failure of the abdominal wall. Reported IH incidence varies among studies. This review presented an overview of definitions, molecular basis, risk factors, incidence, clinical presentation, surgical techniques, postoperative care, cost, risk prediction tools, and proposed preventative measures. A literature search of PubMed was conducted to include high-quality studies on IH. The incidence of IH depends on the primary surgical pathology, incision site and extent, associated medical comorbidities, and risk factors. The review highlighted inherent and modifiable risk factors. The disorganisation of the extracellular matrix, defective fibroblast functions, and ratio variations of different collagen types are implicated in molecular mechanisms. Elective repair of IH alleviates symptoms, prevents complications, and improves the quality of life (QOL). Recent studies introduced risk prediction tools to implement preventative measures, including suture line reinforcement or prophylactic mesh application in high-risk groups. Elective repair improves QOL and prevents sinister outcomes associated with emergency IH repair. The watchful wait strategy should be reviewed, and options should be discussed thoroughly during patients' counselling. Risk stratification tools for predicting IH would help adopt prophylactic measures.

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Section: Aetiology and Molecular Basissupporting

confidence: 80%

Incisional Hernia: A Surgical Complication or Medical Disease?

Omar,

Zaimis,

Townsend

et al. 2023

Cureus

View full text Add to dashboard Cite

show abstract

“…Apart from the decreased amount of collagen, the ratio abnormality of collagen isoforms (collagen I and collagen III) is also evident in both the primary and secondary hernias [ 43 ]. Growth factors [ 44 ], nutrition [ 45 ], and alterations in cell phenotypes [ 46 ] are possible mechanisms of hernia occurrence. Regarding the cellular population taking part in the process, fibroblasts are the most recognized cells that play critical roles in the ECM integrity and mechanical stretching of the abdominal wall [ 47 ].…”

Section: Abdominal Hernia Pathogenesismentioning

confidence: 99%

Abdominal wall hernia repair: from prosthetic meshes to smart materials

Saiding,

Chen,

Wang

et al. 2023

Materials Today Bio

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“…We hypothesized that HMGB1 antagonists inhibit the proliferation and function of fibroblasts, through which inflammation and pruritus are improved in the AD mouse model. We used three biomarkers of α smooth muscle actin (α-SMA) [21], Hsp47, a collagen-specific chaperon with a crucial role in collagen folding [22], and vimentin, an integrator during wound healing and fibroblast proliferation [23], to assay the three proteins in the AD mouse model. Immunohistochemistry of the mouse ears showed that the ratios of α-SMA, Hsp47, and vimentin-positive cells were significantly reduced in glycyrrhizin group as compared to those in the saline group (Fig.…”

Section: Hmgb1 Antagonist Glycyrrhizin Inhibits Proliferation and Sec...mentioning

confidence: 99%

Blockade of HMGB1 Reduces Inflammation and Pruritus in Atopic Dermatitis by Inhibiting Skin Fibroblasts Activation

Zhou,

Yuan,

et al. 2023

Int Arch Allergy Immunol

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Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsed eczema and serious pruritus. High-mobility group box 1 protein (HMGB1) is a nuclear-binding protein and serves as an alarmin to promote inflammatory responses. Methods: In this study, we established an AD mouse model by topical use of MC903 on ears and then used a specific HMGB1-binding peptide cIY8 and a HMGB1 inhibitor of glycyrrhizin to investigate HMGB1 on fibroblast activation in the pathogenesis of AD-like symptoms. Results: Topical use of cIY8 and oral use of glycyrrhizin significantly improved the MC903-induced AD-like symptoms and pathological changes of the ears and scratching behavior in an AD mouse model; cIY8 treatment inhibited the higher mRNAs of IL-1α, IL-4, IL-5, IL-13, and IL-31 in the ears. In human fibroblasts, HMGB1 caused nuclear translocation of NF-kB, and the nuclear translocation could be inhibited by pre-treatment of HMGB1 with cIY8, suggesting that NF-κB signaling pathway participates in the HMGB1-induced inflammation of AD in fibroblasts and that cIY8 effectively impedes the function of HMGB1. Glycyrrhizin inhibited the Ca2+ signaling induced by ionomycin in mouse primary fibroblasts. The fibroblast-related proteins of α-SMA, Hsp47, and vimentin and the pruritus-related proteins of IL-33 and periostin were increased in the ears of the AD mouse model, the ratio of EdU incorporation became higher in mouse fibroblasts treated with MC903, and the higher proliferation and inflammatory responses of the fibroblasts could be reversed by glycyrrhizin treatment. Conclusions: Fibroblast activation by HMGB1 is one of the critical processes in the development of inflammation and pruritus in the AD mouse model. The specific HMGB1-binding peptide cIY8 and the HMGB1 inhibitor glycyrrhizin inactivate skin fibroblasts to alleviate the inflammation and pruritus in the AD mouse model. Peptide cIY8 may be topically used to treat AD patients in the future.

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Biomarkers and heterogeneous fibroblast phenotype associated with incisional hernia

Cited by 13 publications

References 35 publications

Incisional Hernia: A Surgical Complication or Medical Disease?

Incisional Hernia: A Surgical Complication or Medical Disease?

Abdominal wall hernia repair: from prosthetic meshes to smart materials

Blockade of HMGB1 Reduces Inflammation and Pruritus in Atopic Dermatitis by Inhibiting Skin Fibroblasts Activation

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