Keloids: Animal models and pathologic equivalents to study tissue fibrosis

Marttala, Jaana; Andrews, Jonathan; Rosenbloom, Joel; Uitto, Jouni

doi:10.1016/j.matbio.2016.01.014

Cited by 49 publications

(42 citation statements)

References 44 publications

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“…Various animal models for wound healing and fibrosis in general (since there is no known specific animal model for keloids) have previously been extensively reviewed elsewhere. [16][17][18] Such animal models are best suited to pharmacological treatments, because biochemical and histological changes can be observed before and after the treatment, and these results can further provide substantial information to set up clinical trials in humans. 19 Animal models can also provide valuable information on keloid pathophysiology and treatment possibilities.…”

Section: Background Informationmentioning

confidence: 99%

In VitroandEx VivoModels for Functional Testing of Therapeutic Anti-scarring Drug Targets in Keloids

Sharma

Lebeko

Kidzeru

et al. 2019

Advances in Wound Care

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Keloids are benign fibro-proliferative raised dermal lesions that spread beyond the original borders of the wound, continue to grow, rarely regress, and are the most common in pigmented individuals after an abnormal wound healing response. The current treatment failure and respective challenges involved highlighting the underlying issue that the etiopathogenesis of keloids is still not well understood. Disease models are required to better understand the disease pathogenesis. It is not possible to establish keloids in animals because of the uniqueness of this disease to human skin. To address this challenge, along these lines, non-animal reproducible models are vital in investigating molecular mechanisms of keloid pathogenesis and therapeutics development. Recent Advances: Various non-animal models have been developed to better understand the molecular mechanisms involved in keloid scarring and aid in identifying and evaluating the therapeutic potential of novel drug candidates. In this scenario, the current review aims at describing in vitro monocultures, co-cultures, organotypic cultures, and ex vivo whole skin keloid tissue organ culture models. Critical Issues and Future Directions: Current treatment options for keloids are far from securing a cure or preventing disease recurrence. Identifying universally accepted effective therapy for keloids has been hampered by the absence of appropriate disease model systems. Animal models do not accurately mimic the disease, thus non-animal model systems are pivotal in keloid research. The use of these models is essential not only for a better understanding of disease biology but also for identifying and evaluating novel drug targets.

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Section: Background Informationmentioning

confidence: 99%

In VitroandEx VivoModels for Functional Testing of Therapeutic Anti-scarring Drug Targets in Keloids

Sharma

Lebeko

Kidzeru

et al. 2019

Advances in Wound Care

View full text Add to dashboard Cite

show abstract

“…Interestingly, the strength of our LCM approach was demonstrated in the accuracy of in situ differential gene expression between keloid and normal skin compared with monolayer culture, which minimised the degree of gene upregulation in keloid versus normal skin dermis. However, given the complex nature of keloid disease and the fact that there is no validated animal model for keloid disease (33), the in vitro experiments are essential to confirm in situ observations made in human keloid disease tissue in order to progress towards mechanistic understanding of the pathogenesis.…”

Section: In Situ Keloid Dermis and Cultured Keloid Fibroblasts Showedmentioning

confidence: 99%

A Role for Neuregulin-1 in Promoting Keloid Fibroblast Migration via ErbB2-mediated Signaling

Jumper¹,

Hodgkinson²,

Paus³

2017

Acta Derm Venerol

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Keloid disease is a fibroproliferative tumour characterised by aggressive local invasion, evident from a clinically and histologically active migrating margin. During combined laser capture microdissection and microarray analysis-based in situ gene expression profiling, we identified upregulation of the polypeptide growth factor neuregulin-1 (NRG1) and ErbB2 oncogene in keloid margin dermis, leading to the hypothesis that NRG1 contributed to keloid margin migration through ErbB2-mediated signalling. The aim of this study was to probe this hypothesis through functional in vitro studies. Exogenous NRG1 addition to keloid and normal skin fibroblasts altered cytokine expression profiles, significantly increased in vitro migration and keloid fibroblast Src and protein tyrosine kinase 2 (PTK2/FAK) gene expression. ErbB2 siRNA knockdown attenuated both keloid fibroblast migration and Src/PTK2 expression, which were not recovered following NRG1 administration, suggesting the NRG1/ErbB2/Src/PTK2 signaling pathway may be a novel regulator of keloid fibroblast migration, and representing a potential new therapeutic target.

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“…Certain regulators of the fibrotic cascade, such as transforming growth factor β (TGF-β) and fibronectin extra domain A (Fn-EDA) have been demonstrated to play a role in collagen deposition during keloid development, but how they are involved in the initiation and subsequent continuation of collagen deposition has remained unclear. Complicating matters has been the lack of appropriate animal models in which to study keloid development and potential treatment modalities [4]. …”

Section: Introductionmentioning

confidence: 99%

Keloids: The paradigm of skin fibrosis — Pathomechanisms and treatment

et al. 2016

Self Cite

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Keloids, fibroproliferative dermal tumors with effusive accumulation of extracellular matrix (ECM) components, particularly collagen, result from excessive expression of growth factors and cytokines. The etiology of keloids is unknown but they occur after dermal injury in genetically susceptible individuals, and they cause both physical and psychological distress for the affected individuals. Several treatment methods for keloids exist, including the combination therapy of surgical incision followed by intralesional steroid therapy, however, they have high recurrence rate regardless of the current treatment method. Improved understanding of the pathomechanisms leading to keloid formation will hopefully identify pathways that serve as specific targets to improve therapy for this devastating, currently intractable, disorder.

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Keloids: Animal models and pathologic equivalents to study tissue fibrosis

Cited by 49 publications

References 44 publications

In VitroandEx VivoModels for Functional Testing of Therapeutic Anti-scarring Drug Targets in Keloids

In VitroandEx VivoModels for Functional Testing of Therapeutic Anti-scarring Drug Targets in Keloids

A Role for Neuregulin-1 in Promoting Keloid Fibroblast Migration via ErbB2-mediated Signaling

Keloids: The paradigm of skin fibrosis — Pathomechanisms and treatment

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