Keloid fibroblasts have elevated and dysfunctional mechanotransduction signaling that is independent of TGF-β

Deng, Zhenjun; Subilia, Manon; Chin, Ian L.; Hortin, Nicole; Stevenson, Andrew; Wood, Fiona; Prêle, Cecilia M.; Choi, Yu Suk; Fear, Mark W.

doi:10.1016/j.jdermsci.2021.09.002

Cited by 17 publications

(15 citation statements)

References 44 publications

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“…After culturing for about 14 days, adherent growing primary fibroblasts were digested with trypsin (Gibco, 25 200 072, USA). Fibroblasts were cultured in DMEM with high glucose containing 10% foetal bovine serum at 37°C under a 5% CO 2 atmosphere 9,29,30 . Fibroblasts from passages 3 through 7 were used in this study.…”

Section: Methodsmentioning

confidence: 99%

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TSP1 promotes fibroblast proliferation and extracellular matrix deposition via the IL6/JAK2/STAT3 signalling pathway in keloids

Feng

Chen

et al. 2022

Experimental Dermatology

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Keloids are regarded as benign fibroproliferative diseases with unknown pathogenesis that only occur in humans. Keloid tissue proliferates abnormally and bulges beyond the edge of the skin lesion.Keloid tissue not only affects the appearance and causes pain and itching but also causes physical and mental illness in patients. 1 Keloids are characterized by fibroblast proliferation and excessive collagen deposition in the dermis. 2 Although several factors, such as hyperactive inflammation, genetic predisposition, cell heterogeneity and tension, have been shown to play crucial roles in keloid development, the pathogenesis of keloids is still unclear. 3,4 It has been reported that multiple signalling pathways are involved in the pathogenesis of keloids. For instance, the overactive TGFβ-SMAD signalling pathway is the most studied, and it stimulates collagen synthesis and fibroblast proliferation by interacting with

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Section: Methodsmentioning

confidence: 99%

“…Fibroblasts were cultured in DMEM with high glucose containing 10% foetal bovine serum at 37°C under a 5% CO 2 atmosphere. 9,29,30 Fibroblasts from passages 3 through 7 were used in this study.…”

Section: Primary Fibroblast Culturementioning

confidence: 99%

TSP1 promotes fibroblast proliferation and extracellular matrix deposition via the IL6/JAK2/STAT3 signalling pathway in keloids

Feng

Chen

et al. 2022

Experimental Dermatology

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“…Keloid fibroblasts were previously shown to exhibit an amplified response to mechanical strain compared with normal fibroblasts, and their altered mechanotransduction has been linked with expression of α-SMA in vitro. 16,40 This may contribute to the increased average expression of ACTA2 in keloid versus normal fibroblasts in vitro that was observed in the current study. Taken together, the data suggest that α-SMA-negative keloid fibroblasts may adopt a myofibroblast-like phenotype when placed in in-vitro culture.…”

Section: Discussionmentioning

confidence: 72%

Myofibroblasts Are Not Characteristic Features of Keloid Lesions

Hahn

McFarland

Combs

et al. 2022

Plastic and Reconstructive Surgery - Global Open

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Background: Keloids are disfiguring, scar-like lesions that are challenging to treat, with low response rates to current interventions and frequent recurrence. It has been widely reported that keloids are characterized by myofibroblasts, specialized contractile fibroblasts that express alpha-smooth muscle actin (α-SMA). However, evidence supporting a role for myofibroblasts in keloid pathology is inconclusive, with conflicting reports in the literature. This complicates development of more effective therapies, as the benefit of interventions targeting myofibroblasts is unclear. This study was undertaken to determine whether myofibroblasts can be considered characteristic of keloids. Methods: Myofibroblasts in tissue sections from keloids, hypertrophic scars (HTSs), and normal skin were localized by α-SMA immunostaining. Expression of α-SMA mRNA (ACTA2 gene) in normal skin and keloid tissue, and in fibroblasts from normal skin, keloid, and HTSs, was measured using quantitative polymerase chain reaction. Results: Normal skin did not exhibit α-SMA-expressing myofibroblasts, but myofibroblasts were identified in 50% of keloids and 60% of HTSs. No significant differences in ACTA2 expression between keloid and normal skin tissue were observed. Mean ACTA2 expression was higher in HTS (2.54-fold, P = 0.005) and keloid fibroblasts (1.75-fold, P = 0.046) versus normal fibroblasts in vitro. However, α-SMA expression in keloids in vivo was not associated with elevated ACTA2 in keloid fibroblasts in vitro. Conclusions: Despite elevated ACTA2 in cultured keloid fibroblasts, myofibroblast presence is not a consistent feature of keloids. Therefore, therapies that target myofibroblasts may not be effective for all keloids. Further research is required to define the mechanisms driving keloid formation for development of more effective therapies.

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“…There has been a very important association between ASPN and fibrosis in previous studies, but the relationship between keloids and ASPN has been sparsely studied ( Huang S et al, 2022 ; Liu L et al, 2021 ; Tanaka, 2022 ). Due to the rapid development of mechanical biology and the research on the formation and progress of keloids promoted by mechanical forces, the ECM molecular ASPN can also become an effective therapeutic target ( Huang C et al, 2012a ; Huang C et al, 2012b ; Huang C et al, 2013 ; Deng Z et al, 2021 ; Syed F et al, 2012). Keloid are also strongly associated with fibroplasia ( Huang C et al, 2014 ; Huang and Ogawa, 2020 ; Jonathan et al, 2016 ; DorothySupp et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of nanoparticle-mediated siRNA-ASPN as a key gene target in the treatment of keloids

Dong

Zhang²,

Zhang³

et al. 2022

Front. Bioeng. Biotechnol.

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Background: Keloid, also known as connective tissue hyperplasia, is a benign proliferative disorder with a global distribution. The available therapeutic interventions are steroid injections, surgical removal of keloids, radiotherapy, compression therapy, the application of cryosurgery, and many other methods.Objectives: Existing treatments or approaches for keloids may lead to similar or even larger lesions at the site of keloid excision, leading to a high recurrence rate. Therefore, this study aims at identifying a new gene-based therapy for the treatment of keloids.Methods: An ASPN-siRNA/nanoparticle combination (si-ASPN) and a negative siRNA/nanoparticle complex (NC) was developed on the basis of bioinformatics studies and used in vitro and in vivo experiments.Results: The results showed a strong correlation between the development of keloids and high expression of ASPN protein. With the expression of ASPN protein greatly reduced in keloid fibroblasts and nude mice allografts after treatment with si-ASPN, the collagen and fibroblasts were also uniform, thinner, parallel and regular.Conclusion: All the above experimental results suggest that keloid and ASPN are closely related and both fibroblast growth and metabolism of keloid are inhibited after silencing ASPN. Therefore, ASPN-siRNA delivered via nanoparticles can serve as a novel intervention therapy for the treatment of keloids.

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Keloid fibroblasts have elevated and dysfunctional mechanotransduction signaling that is independent of TGF-β

Cited by 17 publications

References 44 publications

TSP1 promotes fibroblast proliferation and extracellular matrix deposition via the IL6/JAK2/STAT3 signalling pathway in keloids

TSP1 promotes fibroblast proliferation and extracellular matrix deposition via the IL6/JAK2/STAT3 signalling pathway in keloids

Myofibroblasts Are Not Characteristic Features of Keloid Lesions

Identification of nanoparticle-mediated siRNA-ASPN as a key gene target in the treatment of keloids

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