Improvement of hypertrophic scarring by using topical anti‐fibrogenic/anti‐inflammatory factors in a rabbit ear model

Rahmani-Neishaboor, Elham; Yau, Farrah Meng-kay; Jalili, Reza B.; Kilani, Ruhangiz T.; Ghahary, Aziz

doi:10.1111/j.1524-475x.2010.00598.x

Cited by 43 publications

(75 citation statements)

References 25 publications

(41 reference statements)

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“…They also showed that collagenase mRNA expression and activity in the fibroblast conditioned medium is significantly reduced in HSC fibroblasts compared to the normal ones [4]. Recent studies [5], [6], [7] demonstrate that localized application of agents that are targeted to suppress matrix accumulation provide an approach to specifically reduce scarring.…”

Section: Introductionmentioning

confidence: 99%

Anti-Scarring Properties of Different Tryptophan Derivatives

et al. 2014

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Hypertrophic scars are associated with prolonged extracellular matrix (ECM) production, aberrant ECM degradation and high tissue cellularity. Routinely used antifibrotic strategies aim to reduce ECM deposition and enhance matrix remodeling. Our previous study investigating the antifibrotic effects of indoleamine2, 3 dioxygenase (IDO) led to the identification of kynurenine (Kyn) as an antiscarring agent. A topical antifibrogenic therapy using Kyn is very attractive; however, it is well established that Kyn passes the blood brain barrier (BBB) which causes complications including excitatory neuronal death. Here we investigated the antiscarring properties of kynurenic acid (KynA), a downstream end product of Kyn that is unlikely to pass the BBB, as an effective and safe replacement for Kyn. Our results indicated that while not having any adverse effect on dermal cell viability, KynA significantly increases the expression of matrix metalloproteinases (MMP1 and MMP3) and suppresses the production of type-I collagen and fibronectin by fibroblasts. Topical application of cream containing KynA in fibrotic rabbit ear significantly decreased scar elevation index (1.13±0.13 vs. 1.61±0.12) and tissue cellularity (221.38±21.7 vs. 314.56±8.66 cells/hpf) in KynA treated wounds compared to controls. KynA treated wounds exhibited lower levels of collagen deposition which is accompanied with a significant decrease in type-I collagen and fibronectin expression, as well as an increase in MMP1 expression compared to untreated wounds or wounds treated with cream only. The results of this study provided evidence for the first time that KynA is promising candidate antifibrogenic agent to improve healing outcome in patients at risk of hypertrophic scarring.

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Section: Introductionmentioning

confidence: 99%

Anti-Scarring Properties of Different Tryptophan Derivatives

et al. 2014

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“…These results suggested that overexpressed miR-185 can inhibit HSFBs growth and that the underlying mechanism was mediated, at least partly, through the suppression of TGF-β1 and Col-1 expression. HS occurs as a result of a pathological wound-healing process, characterized by excess collagen deposition and hyperproliferation of fibroblasts (2,6,8). …”

Section: Discussionmentioning

confidence: 99%

“…During the inflammatory phase of healing, chemotactic and inflammatory factors are induced, which are the prerequisites for subsequent processes, including angiogenesis, re-epithelialization, recruitment, the proliferation of fibroblasts and extracellular matrix (ECM) deposition (7,8). Fibroblasts recruitment and proliferation, the production of ECM, and the inhibition of the production of proteases required to maintain the balance between production and degradation, are influenced predominantly by the fibrogenic growth factors, including insulin-like growth factor, platelet-derived growth factor and transforming growth factor-β (TGF-β) (6).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-185 regulates transforming growth factor-β1 and collagen-1 in hypertrophic scar fibroblasts

Xiao

Luo

Wang

et al. 2017

Molecular Medicine Reports

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Transforming growth factor-β1 (TGF-β1) and collagen type I (Col-1) serve a critical role in the development and progression of hypertrophic scarring (HS). The present study hypothesized that a post-translational mechanism of microRNAs (miR) regulated the expression of TGF-β1 and Col-1 in HS fibroblasts (HSFBs). A collection of 20 HS tissues was compared with corresponding normal tissues from clinical patients, and the expression of miR-185 was measured. Using PicTar, TargetScan and miRBase databases, it was identified that miR-185 may be a regulator of TGF-β1 and Col-1 in humans. Based on these hypotheses, the expression of miR-185, TGF-β1 and Col-1 in HS tissues was investigated. The results demonstrated that the expression of miR-185 was markedly suppressed, and TGF-β1 and Col-1 levels were increased, in HS tissues. The expression levels of endogenous miR-185 negatively correlated with the TGF-β1 and Col-1 mRNA levels (Pearson's correlation coefficient r=−0.674, P<0.01 and r=−0.590, P<0.01, respectively). In vitro, miR-185 can regulate TGF-β1 and Col-1 through the predicted binding sites in its 3′-untranslated region. miR-185 had an effect on cell proliferation and apoptosis, thereby regulating HSFBs growth. In addition, miR-185 gain-of-function decreased TGF-β1 and Col-1 protein expression, and miR-185 loss-of-function increased TGF-β1 and Col-1 protein expression in HSFBs. In conclusion, overexpressed miR-185 could inhibit HSFBs growth, and the underlying mechanism was mediated, at least partly, through the suppression of TGF-β1 and Col-1 expression. However, above all, miR-185 might serve as a potential therapeutic approach for the treatment of HS.

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“…Finally the tissue was dehydrated, cleared and sealed. Collagen deposition was evaluated by the Image Pro Plus 4.5 software and the relative density of collagen in each group was counted by normalizing to the collagen density in the control group [17]. …”

Section: Methodsmentioning

confidence: 99%

Compound Astragalus and Salvia miltiorrhiza Extract Suppresses Rabbits' Hypertrophic Scar by Modulating the TGF-β/Smad Signal

Jiang²,

Boye³

et al. 2014

Dermatology

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Background: Hypertrophic scar is a fibro-proliferative disease. Our previous studies demonstrate that compound Astragalus and Salvia miltiorrhiza extract (CASE) inhibits proliferation and invasion in keloid fibroblasts. Objective: To investigate the effects of CASE on hypertrophic scar. Methods: Rabbits were divided into the control, model and three dosage groups of CASE (0.94, 1.88, 3.76%). An animal model of hypertrophic scar was established and treated with CASE ointment or ointment base. The histopathological detection by hematoxylin & eosin and Masson's trichrome staining and protein expression of scars by Western blot were performed. Results: The hydroxyproline content was decreased under CASE treatment. Transforming growth factor beta 1 (TGF-β₁) protein expression increased in the model group while it decreased under CASE treatment. The elevated expression of Smad4 protein was decreased under CASE treatment. Additionally, CASE promoted Smad7 protein expression. Conclusion: CASE could inhibit formation of hypertrophic scar by modulating TGF-β/Smad signal and may be useful for the treatment of hyperplastic scars.

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Improvement of hypertrophic scarring by using topical anti‐fibrogenic/anti‐inflammatory factors in a rabbit ear model

Cited by 43 publications

References 25 publications

Anti-Scarring Properties of Different Tryptophan Derivatives

Anti-Scarring Properties of Different Tryptophan Derivatives

MicroRNA-185 regulates transforming growth factor-β1 and collagen-1 in hypertrophic scar fibroblasts

Compound <b><i>Astragalus</i></b> and <b><i>Salvia miltiorrhiza</i></b> Extract Suppresses Rabbits' Hypertrophic Scar by Modulating the TGF-β/Smad Signal

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