Hypertension: a systemic key to understanding local keloid severity

Arima, Juri; Huang, Chenyu; Rosner, Bernard; Akaishi, Satoshi; Ogawa, Rei

doi:10.1111/wrr.12277

Cited by 71 publications

(78 citation statements)

References 39 publications

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“…Our recent study also showed that hypertension associates with the development of severe keloids [9]. That study assessed whether hypertension, a circulating factor, influences local keloid severity.…”

Section: Systemic Risk Factors That Increase Dermal Inflammationmentioning

confidence: 99%

Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis

Ogawa

2017

IJMS

Self Cite

632

616

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Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloidal and hypertrophic scarring. This suggests that these pathological scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. The latter is characterized by continuous and histologically localized inflammation. As a result, the reticular layer of keloids and hypertrophic scars contains inflammatory cells, increased numbers of fibroblasts, newly formed blood vessels, and collagen deposits. Moreover, proinflammatory factors, such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α are upregulated in keloid tissues, which suggests that, in patients with keloids, proinflammatory genes in the skin are sensitive to trauma. This may promote chronic inflammation, which in turn may cause the invasive growth of keloids. In addition, the upregulation of proinflammatory factors in pathological scars suggests that, rather than being skin tumors, keloids and hypertrophic scars are inflammatory disorders of skin, specifically inflammatory disorders of the reticular dermis. Various external and internal post-wounding stimuli may promote reticular inflammation. The nature of these stimuli most likely shapes the characteristics, quantity, and course of keloids and hypertrophic scars. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. These observations together suggest that the clinical differences between keloids and hypertrophic scars merely reflect differences in the intensity, frequency, and duration of the inflammation of the reticular dermis. At present, physicians cannot (or at least find it very difficult to) control systemic and genetic risk factors of keloids and hypertrophic scars. However, they can use a number of treatment modalities that all, interestingly, act by reducing inflammation. They include corticosteroid injection/tape/ointment, radiotherapy, cryotherapy, compression therapy, stabilization therapy, 5-fluorouracil (5-FU) therapy, and surgical methods that reduce skin tension.

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Section: Systemic Risk Factors That Increase Dermal Inflammationmentioning

confidence: 99%

Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis

Ogawa

2017

IJMS

Self Cite

632

616

View full text Add to dashboard Cite

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“…3,4 Individuals under age 30 with keloids have a higher incidence of hypertension. 5,6 Our results are consistent with previously reported findings and invite further inquiry into the systemic similarities between hypertension and keloid pathogenesis.…”

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confidence: 99%

A case–control study analyzing the association of keloids with hypertension and obesity

Rutherford

Glass

2017

Int J Dermatology

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“…Sex hormones such as estrogen and androgen, which have vasodilatory effects, have been suggested to affect the inflammatory response in keloids, as reflected by the higher risk of keloid development during adolescence and pregnancy [14]. Another factor associated with keloid development is hypertension, which could be attributed to the effect of hypertension on increasing inflammation by damaging blood vessels [15,16]. Mechanical forces play an important role in keloid development, and several surgical techniques are being developed to reduce the mechanical forces around keloids [8].…”

Section: Introductionmentioning

confidence: 99%

Growth Differentiation Factor-9 Promotes Fibroblast Proliferation and Migration in Keloids through the Smad2/3 Pathway

Jiang

Yu²,

Xia³

et al. 2016

Cell Physiol Biochem

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Background: Keloids are fibroproliferative scars that develop as a result of a dysregulated wound healing process; however, the molecular mechanisms of keloid pathogenesis remain unclear. Keloids are characterized by the ability to spread beyond the original boundary of the wound, and they represent a significant clinical challenge. Previous work from our group suggested that growth differentiation factor (GDF)-9 plays a role in the invasive behavior of keloids. Here, we examined the involvement of GDF-9 in keloid formation and spread and elucidated a potential underlying mechanism. Methods: The expression of GDF-9, cyclooxygenase (COX)-2, vascular epidermal growth factor (VEGF)-C, matrix metalloprotease (MMP)-2, MMP-9, transforming growth factor (TGF)-β1, and the related signaling pathway components in human keloid tissues or keloid fibroblasts (kFBs) was monitored by qRT-PCR and western blot. A series of overexpression and silencing experiments in normal and keloid fibroblasts were used to modify the expression of GDF-9. The effects of GDF-9 on kFB proliferation and migration were assessed using the CCK-8, cell cycle and scratch wound healing assays. Results: GDF-9 promotes fibroblast proliferation and migration. GDF-9 silencing in kFBs decreased cell proliferation, blocked cell cycle progression, downregulated the angiogenic markers COX-2 and VEGF-C, and downregulated MMP-2 and MMP-9 expression, whereas it had no effect on the levels of TGF-β1. GDF-9 silencing significantly inhibited Smad2 and Smad3 phosphorylation in kFBs. Conclusions: GDF-9 promotes the proliferation and migration of kFBs via a mechanism involving the Smad2/3 pathway.

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Hypertension: a systemic key to understanding local keloid severity

Cited by 71 publications

References 39 publications

Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis

Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis

A case–control study analyzing the association of keloids with hypertension and obesity

Growth Differentiation Factor-9 Promotes Fibroblast Proliferation and Migration in Keloids through the Smad2/3 Pathway

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