Resveratrol inhibits fibrogenesis and induces apoptosis in keloid fibroblasts

Ikeda, Kimiyuki; Torigoe, Toshihiko; Matsumoto, Yoshitaka; Fujita, Tatsuya; Sato, Noriyuki; Yotsuyanagi, Takatoshi

doi:10.1111/wrr.12062

Cited by 43 publications

(29 citation statements)

References 36 publications

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“…The up‐regulation of SIRT1 by its agonist resveratrol has been shown to inhibit the renal fibrosis, liver fibrosis and pulmonary fibrosis induced by bleomycin (Lee et al , ; Akgedik et al , ; Liang et al , ). Furthermore, Ikeda et al () reported that in keloid‐derived fibroblasts, resveratrol significantly down‐regulates the expression of Col1, α‐SMA and TGF‐β1. However, the proliferation of fibroblasts also decreased after stimulation with resveratrol (Ikeda et al , ).…”

Section: Discussionmentioning

confidence: 99%

Identification of sirtuin 1 as a promising therapeutic target for hypertrophic scars

Bai

Liu

Yang

et al. 2016

British J Pharmacology

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*These authors contributed equally to this work. BACKGROUND AND PURPOSESirtuin1 (SIRT1), the founding member of mammalian class III histone deacetylases, is reported to be a drug target involved in fibrotic diseases. However, whether it is an effective drug target in hypertrophic scar treatment is still not known. EXPERIMENTAL APPROACHIn the present study, we observed that SIRT1 localized to both the epidermis and the dermis of skin tissues by immunohistochemistry. After knock-down of SIRT1 by shRNA or up-regulating SIRT1 by resveratrol, the expression of α-SMA, Col1 and Col3 in fibroblasts were detected by western blots. A mouse excision wound healing model was used to observe the changes in collagen fibre associated with the different expression levels of SIRT1. KEY RESULTSSIRT1 expression was inhibited in hypertrophic scar tissue. The down-regulation of SIRT1 resulted in an increased expression of α-SMA, Col1 and Col3 in hypertrophic scar-derived fibroblasts. In contrast, the up-regulation of SIRT1 not only inhibited the expression of α-SMA, Col1 and Col3 in hypertrophic scar-derived fibroblasts but also blocked the activation of TGFβ1-induced normal skin-derived fibroblasts. In the mouse model of wound healing, the deletion of SIRT1 resulted in denser collagen fibres and a more disordered structure, whereas resveratrol treatment led to a more organized and thinner collagen fibre, which was similar to that observed during normal wound healing. CONCLUSIONS AND IMPLICATIONSThe results revealed that SIRT1 negatively regulates TGFβ1-induced fibroblast activation and inhibits excessive scar formation and is, therefore, a promising drug target for hypertrophic scar formation. IntroductionHypertrophic scars are characterized by the excessive production and deposition of extracellular matrix (ECM) proteins. They usually develop after burn injury, trauma and surgery, and cause not only cosmetic but also functional problems (Gurtner et al., 2008;Hsu et al., 2010;Gauglitz et al., 2011;Tyack et al., 2012). Although extensively studied, the mechanism of hypertrophic scar formation is still currently unclear, and treatment remains a great challenge. It is widely accepted that the major characteristic of hypertrophic scars is the excessive deposition of collagen-based ECM proteins. Under normal conditions, the dynamic balance between the synthesis and degradation of collagen is regulated by matrix metalloproteinase, tissue inhibitor of metalloproteinase and various cytokines, such as TGFβ1. The balance is broken after skin injuries, which leads to increased synthesis and deposition of collagen, and the skin then recovers and becomes normal after wound healing (Sternlicht and Werb, 2001;Park et al., 2004;Armour et al., 2007). However, prolonged inflammation and other chronic stimuli may result in the overproduction of collagen, finally leading to hypertrophic scar formation (Armour et al., 2007;van der Veer et al., 2009).Among the various cell types in skin, fibroblasts are responsible for the synthesis of collagen and othe...

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Section: Discussionmentioning

confidence: 99%

Identification of sirtuin 1 as a promising therapeutic target for hypertrophic scars

Bai

Liu

Yang

et al. 2016

British J Pharmacology

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“…Previous studies have found that transresveratrol inhibits collagen production in cultures of intestinal fibroblasts [40] [41]. When evaluating the effects of trans-resveratrol on the treatment of keloids, Ikeda et al [42] found that trans-resveratrol did not decrease the amount of type I collagen on normal skin, and might have an antifibrogenic effect on keloid fibroblasts without adversely affecting the fibroblasts in normal skin. Kundu et al [43] found that the suppression of COX-2 expression by blocking the activation of MAPKs and AP-1 may also represent a possible molecular mechanism for previously reported anti-tumor promoting effects of trans-resveratrol on mouse skin carcinogenesis.…”

Section: Resultsmentioning

confidence: 99%

Formulations Containing Curcumin or Trans-Resveratrol Increase Dermal Thickness in Rats Submitted to Chemical Peeling

Gonçalves¹,

Barros²,

Silva³

et al. 2017

JCDSA

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Plant-derived substances such as curcumin and trans-resveratrol, both of which have anti-inflammatory properties, may have a beneficial effect on human skin. The present study analyzed the effects of topical formulations containing curcumin or trans-resveratrol on the recovery and rejuvenation of skin after chemical peeling. The study was performed on rats, randomly divided into seven groups of six animals each. Superficial peeling was performed using a 50% glycolic acid gel, which was applied to the dorsal region of each animal. Rats were then treated with the experimental formulations for 15 days. On the sixteenth day, skin samples were taken and mounted on slides for histological analysis. Statistical analysis showed that the formulation containing transresveratrol led to increased dermal and epidermal thickness, while the formulation containing curcumin had no effects on epidermal thickness. The increased epidermal thickness may reflect greater skin vitality, although this was not directly evaluated. The increase in dermal thickness may be attributed to greater collagen production, which may increase skin firmness and elasticity, and lead to skin rejuvenation as well as wrinkle reduction. Formulations containing curcumin or trans-resveratrol may have potential for the topical treatment after peeling and of sensitive skin, in addition to being used for their antiaging properties.

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“…Meanwhile, resveratrol inhibited the proliferation and induced apoptosis of keloid derived fibroblasts. In an animal model, it was demonstrated that resveratrol decreased the expression of TGF‐β and α‐SMA in fibroblasts derived from scar, but has no effect on fibroblasts under physiological conditions …”

Section: Traditional Plant‐based Medicine and Productsmentioning

confidence: 99%

Biological approaches for hypertrophic scars

Zhong

2019

International Wound Journal

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Scar formation is usually the pathological consequence of skin trauma. And hypertrophic scars (HSs) frequently occur in people after being injured deeply. HSs are unusually considered as the result of tissue contraction and excessive extracellular matrix component deposition. Myofibroblasts, as the effector cells, mainly differentiated from fibroblasts, play the crucial role in the pathophysiology of HSs. A number of growth factors, inflammatory cytokines involved in the process of HS occurrence. Currently, with in‐depth exploration and clinical research of HSs, various creative and effective treatments budded. In here, we summarize the progress in the molecular mechanism of HSs, and review the available biotherapeutic methods for their pathophysiological characteristics. Additionally, we further prospected that the comprehensive therapy may be more suitable for HS treatment.

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Resveratrol inhibits fibrogenesis and induces apoptosis in keloid fibroblasts

Cited by 43 publications

References 36 publications

Identification of sirtuin 1 as a promising therapeutic target for hypertrophic scars

Identification of sirtuin 1 as a promising therapeutic target for hypertrophic scars

Formulations Containing Curcumin or Trans-Resveratrol Increase Dermal Thickness in Rats Submitted to Chemical Peeling

Biological approaches for hypertrophic scars

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