Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review)

Dong, Xiao; Mao, Shaolin; Wen, Hao

doi:10.3892/br.2013.169

Cited by 77 publications

(59 citation statements)

References 33 publications

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“…The process of transition from fibroblasts to myofibroblasts is mainly regulated by transforming growth factor (TGF)-β1 (3). In response to TGF-β1, fibroblasts differentiate into myofibroblasts, which contract the wound and aid in the remodeling of the extracellular matrix (ECM) (4). The major pathway of TGF-β1-induced myofibroblast differentiation is mediated via Smad activation by the TGF-β1 receptor complex, leading to Smad2 and Smad3 complex association with Smad4 and translocation into the nucleus.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway

Zhao

Guan

Liu

et al. 2016

International Journal of Molecular Medicine

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Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial-mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring. The aim of this study was to investigate whether hypoxia drives the transition of dermal fibroblasts to myofibroblasts and to clarify the potential transduction mechanisms involved. First, we observed that keloids are a relatively hypoxic tissue. Second, we found that hypoxia drives the transition of normal dermal fibroblasts to a myofibroblast-like phenotype [high expression of α-smooth muscle actin (α-SMA) and collagen I and III]. Finally, hypoxia effectively facilitated the nuclear import of the Smad2 and Smad3 complex, while blockade with the Smad3 inhibitor, SIS3, significantly impaired the expression of hypoxia-induced fibrosis-related molecules. Taken together, to the best of our knowledge, this study demonstrates for the first time that hypoxia facilitates the transition of dermal fibroblasts to myofibroblasts through the activation of the TGF-β1/Smad3 signaling pathway and our findings may provide a potential target for the treatment of keloids.

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Section: Introductionmentioning

confidence: 99%

Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway

Zhao

Guan

Liu

et al. 2016

International Journal of Molecular Medicine

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“…13 In the normal process of wound healing, the inflammation, granulation formation, and extracellular matrix formation balance are maintained by controlling the fibroblast activity. 14 If the control of fibroblast activity is lost, the coexistent result is either keloid or hypertrophic scars. In addition to gene up-regulation theory of fibroblasts, many studies examine the role of wound tension, sebum secretion, and neurogenic inflammation as predisposing factors of keloid scar formation.…”

Section: Introductionmentioning

confidence: 99%

Novel Insights on Understanding of Keloid Scar: Article Review

Mari

Alsabri

Tabal

et al. 2015

Journal of the American College of Clinical Wound Specialists

123

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Keloid scar, dermal benign fibro-proliferative growth that extends outside the original wound and invades adjacent dermal tissue due to extensive production of extracellular matrix, especially collagen, which caused by over expression of cytokines and growth factors. Although many attempts were made to understand the exact pathophysiology and the molecular abnormalities, the pathogenesis of keloid scar is yet to be determined. Even though there are several treatment options for keloid scars include combination of medical and surgical therapies like combination of surgical removal followed by cryotherapy or intralesional steroid therapy, the reoccurrence rate is still high despite the present treatment. In this review, PubMed, clinical key and Wright State Library web site have been used to investigate any update regarding Keloid disease. We used Keloid, scar formation, hypertrophic scar and collagen as key words. More than 40 articles have been reviewed. This paper reviews literature about keloid scar formation mechanism, the most recent therapeutic options including the ones under research.

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“…(11) With the normal healing of wounds, an influx of inflammatory cells to the wound site occurs until the fourth to sixth day, followed by a proliferative phase, during which the inflammatory cells are replaced by fibroblasts. In long-term, non-healing ischemic wounds, the elements of all three phases can simultaneously be present, but inflammation is predominant.…”

Section: Discussionmentioning

confidence: 99%

Effects of Fibroblast Transplantation on the Content of Macrophages and the Morphology of Regenerating Ischemic Cutaneous Wounds

Shapovalova¹,

Boyko²,

Baranovskiy³

et al. 2017

IJBM

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Background: The study of the morphological structure and the determination of macrophagal fraction (MF) in the newly formed epidermis and dermis on the 19th day after the transplantation of auto-and heterofibroblasts and a dermal equivalent with heterofibroblasts will allow determining the optimal method for ischemic wound healing. Materials and Methods:The study was performed on 28 white mature mice of the C57/B1 line aged between 5 and 7 months. In an ischemic cutaneous wound, 0.4 ml of fibroblast suspension (1.33 million cells) and a dermal equivalent were transplanted. The biopsy material was embedded in paraffin and stained with H&E by the Weigert-Van Gieson method to visualize the elastic and collagen fibers. Macrophages were determined by monoclonal antibodies to CD68. On the 19th day of the healing of ischemic cutaneous wound, the wound healing process goes through the transition from the stage of proliferation with GT formation into the stage of differentiation or fibrosis. The most positive for regenerative histogenesis and inflammation is the introduction of autofibroblasts. The most differentiated epidermis is formed after transplantation into the wound of the dermal equivalent with heterofibroblasts due to the presence of hairpieces in the form of formed hair follicles. The favorable effect of the dermal equivalent with heterofibroblasts differs from the influence of the autofibroblast suspension only by several percent: the thickness of the epidermis by 4.29%, the area of collagen fibers by 2.66%, and the area of the blood vessels by 4.04%. The most positive treatment for regenerative histogenesis and inflammation is the introduction of autofibroblasts. The most differentiated epidermis is formed after transplantation into the wound of the dermal equivalent with heterofibroblasts, due to the presence of pieces hair in the form of formed hair follicles.Conclusion: The favorable effect of the dermal equivalent with heterofibroblasts differs from the influence of the autofibroblast suspension by only several percent: the thickness of the epidermis by 4.29%, the area of collagen fibers by 2.66%, and the area of the blood vessels by 4

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Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review)

Cited by 77 publications

References 33 publications

Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway

Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway

Novel Insights on Understanding of Keloid Scar: Article Review

Effects of Fibroblast Transplantation on the Content of Macrophages and the Morphology of Regenerating Ischemic Cutaneous Wounds

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