Upregulation of TGF-β1 and basic FGF in elastofibroma: an immunohistochemical analysis

Imanishi, Akiko; Imanishi, Hiroyasu; Yoshida, Yasuhiko; Okabayashi, Aya; Tateishi, Chiharu; Ikushima, Hirofumi; Nagasako, Ren; Nakagawa, Kōichi; Tsuruta, Daisuke

doi:10.1007/s00795-015-0126-z

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…TGFβ is typically regarded as a master regulator of fibrotic processes and its three isoforms are capable of exerting different biological functions in a highly cell type-specific and tissue-dependent manner [ 44 ]. TGFβ ligands most commonly form heterotetrameric complexes with TGFβ-RI and -RII, thus propagating signalling to the receptor-activated SMADs (R-SMADs) [ 46 , 47 ]. Phosphorylated R-SMADs interact with the common mediator SMAD4 to form oligomeric complexes that translocate to the nucleus and work as bona fide transcription factors [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Occurrence of Cutaneous Leiomyomas and Dermatofibromas in Patients with Uterine Leiomyomas without Fumarate Hydratase Gene Mutations

et al. 2023

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Leiomyomas are smooth muscle-derived benign neoplasms that can affect all organs, most frequently in the uterus. Fumarate hydratase gene (FH) mutation is characterised by an autosomal dominant disease with increased occurrence of renal tumours, but also by cutaneous (CLs) and uterine leiomyomas (ULs). So far, an increased occurrence of skin tumours in non-mutated patients with ULs has not been verified. To this aim, a case-group of women who were FH non-mutated patients surgically treated for ULs (n = 34) was compared with a control-group (n = 37) of consecutive age-matched healthy women. The occurrence of skin neoplasms, including CLs and dermatofibromas (DFs), was evaluated. Moreover, the microscopic features of FH non-mutated skin tumours were compared with those of an age-matched population group (n = 70) who presented, in their clinical history, only one type of skin tumour and no ULs. Immunohistochemical and in vitro studies analysed TGFβ and vitamin D receptor expression. FH non-mutated patients with ULs displayed a higher occurrence of CLs and DFs (p < 0.03 and p < 0.001), but not of other types of skin tumours. Immunohistochemistry revealed a lower vitamin D receptor (VDR) expression in CLs and DFs from the ULs group compared with those from the population group (p < 0.01), but a similar distribution of TGFβ-receptors and SMAD3. In vitro studies documented that TGFβ-1 treatment and vitamin D3 have opposite effects on α-SMA, TGFβR2 and VDR expression on dermal fibroblast and leiomyoma cell cultures. This unreported increased occurrence of CLs and DFs in FH non-mutated patients with symptomatic ULs with vitamin D deficiency suggests a potential pathogenetic role of vitamin D bioavailability also for CLs and DFs.

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Section: Discussionmentioning

confidence: 99%

Increased Occurrence of Cutaneous Leiomyomas and Dermatofibromas in Patients with Uterine Leiomyomas without Fumarate Hydratase Gene Mutations

et al. 2023

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“…This suggests that a high level of stress induces a cellular defense mechanism that leads to growth factor production. FGF-2 also activates odontogenic cysts and tumors (So, Daley, Jackson, & Wysocki, 2001) and increases the proportion of FGF-positive fibroblasts in elastofibroma (Imanishi et al, 2016). Furthermore, drug-induced gingival overgrowth induced EGF production (Chin et al, 2006;Soory & Kasasa, 1997).…”

Section: Discussionmentioning

confidence: 99%

Effects of mechanical stress on human oral mucosa‐derived cells

et al. 2020

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A loss of teeth can cause occlusal disturbance, which may require treatment by dentures. Placement of dentures can cause mechanical stress (MS), such as occlusal pressure, on the oral mucosa. In certain cases, local inflammation of the oral mucosa, manifesting as redness and swelling, can be observed beneath a denture even when the denture is well-fitting, and there is little accumulation of dental plaque on the oral mucosa. Periodontal tissues that are exposed to MS include the periodontal ligament, alveolar bone, and part of gingiva that forms the oral mucosa. Previous studies demonstrated that in response to MS that mimics physiological occlusal pressure, the periodontal ligament induces the production and homeostasis of inflammatory cytokines, in addition to cytokines and growth factors that are involved in wound healing (Ichioka et al., 2016;

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“…Apart from influencing proliferation, IFN‐γ and TA are also known to inhibit collagen synthesis; therefore both active agents are predestined to reduce the imbalanced collagen synthesis in keloids. Both aspects are addressed in anti‐fibrotic treatment regimens in clinical settings to correct the divergent cytokine profile and proportions of collagen type I and collagen type III in keloids compared to healthy skin . Irradiation regimens and application of cytostatic drugs are only some treatment regimens that aspire to reduce the extracellular matrix production while in parallel increasing catabolic processes and reducing cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Normal and keloid fibroblasts are differentially influenced by IFN‐γ and triamcinolone as well as by their combination

Euler

Valesky

Meißner

et al. 2019

Wound Repair Regeneration

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Impaired wound healing as well as imbalanced cell proliferation and extracellular matrix synthesis and degeneration can cause aberrant scarring. The most severe impacts of such scarring on patients' lives are stigmatization and physical restriction. Although, a broad variety of combinatorial approaches with, e.g., glucocorticoids, chemotherapeutics, and immunomodulators are used, there is still a high recurrence rate of keloids. The aim of this study was to investigate which influence interferon γ (IFN-γ, 1.000-10.000 IU/mL) and/or triamcinolone acetonide (TA, 1 μg/mL) have on proliferation, cell viability, collagen type I synthesis, and cytokine secretion in healthy and keloid fibroblasts. It was shown that mono-treatment with IFN-γ or TA for 2 days induced a severe reduction of the proliferative potential in both cell species. The combinatory treatment (IFN-γ plus TA) of keloid fibroblasts enhanced the anti-proliferative effect of the mono-treatments, whereas no additional anti-proliferative effect was observed in normal fibroblasts. Furthermore, we observed that the combinatory treatment regimen reduced the expression of α-smooth muscle actin (α-SMA), an actin isotype contributing to cell-generated mechanical tension, in keloid fibroblasts. In normal fibroblasts, α-SMA was reduced by the mono-treatment with IFN-γ as well as by the combinatory treatment. The analysis of collagen-type I synthesis revealed that TA did not reduce collagen type I synthesis in normal fibroblasts but in keloid fibroblasts. IFN-γ reduced in both cell species the collagen type I synthesis. The combination of TA and IFN-γ intensified the previously observed collagen type I synthesis reduction in keloid fibroblasts. The herein presented data suggest the combinatory application of IFN-γ and TA as a promising therapy concept for keloids.

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Upregulation of TGF-β1 and basic FGF in elastofibroma: an immunohistochemical analysis

Cited by 7 publications

References 9 publications

Increased Occurrence of Cutaneous Leiomyomas and Dermatofibromas in Patients with Uterine Leiomyomas without Fumarate Hydratase Gene Mutations

Increased Occurrence of Cutaneous Leiomyomas and Dermatofibromas in Patients with Uterine Leiomyomas without Fumarate Hydratase Gene Mutations

Effects of mechanical stress on human oral mucosa‐derived cells

Normal and keloid fibroblasts are differentially influenced by IFN‐γ and triamcinolone as well as by their combination

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