Growth factor pathways in hypertrophic scars: Molecular pathogenesis and therapeutic implications

Lian, Naqi; Li, Taiping

doi:10.1016/j.biopha.2016.09.010

Cited by 83 publications

(65 citation statements)

References 102 publications

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“…Various biological properties of both fibroblasts and myofibroblasts have profound impact on the progression and regression of HS. These complex processes are influenced by a signaling network involving different cytokines and growth factors of which are to mention, TGF-β, epidermal growth factor, platelet-derived growth factor, connective tissue growth factor (CTGF), and vascular endothelial growth factor, which is known as a key factor in angiogenesis essential for wound healing (14, 15). The transition from fibroblasts to myofibroblasts expressing α-smooth muscle actin (SMA) is influenced by cytokines, previously listed growth factors, especially TGF-β whose activity diminishes upon the completion of wound repair, mechanical stress, and cellular fibronectin (16).…”

Section: The Critical Role Of Myofibroblasts and Other Ecm Componentsmentioning

confidence: 99%

Current Therapeutic Approach to Hypertrophic Scars

et al. 2017

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Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome.

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Section: The Critical Role Of Myofibroblasts and Other Ecm Componentsmentioning

confidence: 99%

Current Therapeutic Approach to Hypertrophic Scars

et al. 2017

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“…It is found that scar hyperplasia is a common result of overproduction of various cytokines, abnormal proliferation, activation, contraction of fibroblasts, and collagen deposition (Wolfram et al, 2009). Transforming growth factor-beta (TGF-β) plays a critical role on the pathological process of HPS, it mediates fibroblasts proliferation, myofibroblasts differentiation, and extracellular matrix (ECM) deposition, and targeting TGF-β through different pathways can prevent HPS formation (Beanes et al, 2003; Chalmers, 2011; Lian and Li, 2016). …”

Section: Introductionmentioning

confidence: 99%

Honokiol Alleviates Hypertrophic Scar by Targeting Transforming Growth Factor-β/Smad2/3 Signaling Pathway

Zhao

Wang

et al. 2017

Front. Pharmacol.

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Hypertrophic scar (HPS) presents as excessive extracellular matrix deposition and abnormal function of fibroblasts. However, there is no single satisfactory method to prevent HPS formation so far. Here, we found that honokiol (HKL), a natural compound isolated from Magnolia tree, had an inhibitory effect on HPS both in vitro and in vivo. Firstly, HKL could dose-dependently down-regulate the mRNA and protein levels of type I collagen, type III collagen, and α-smooth muscle actin (α-SMA) in hypertrophic scar-derived fibroblasts (HSFs). Secondly, HKL suppressed the proliferation, migration abilities of HSFs and inhibited HSFs activation to myofibroblasts, but had no effect on cell apoptosis. Besides, the in vivo rabbit ear scar model further affirmed the inhibitory effects of HKL on collagen deposition, proliferating cell nuclear antigen and α-SMA. Finally, Western blot results showed that HKL reduced the phosphorylation status of Smad2/3, as well as affected the protein levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase1. Taken together, this study demonstrated that HKL alleviated HPS by suppressing fibrosis-related molecules and inhibiting HSFs proliferation, migration as well as activation to myofibroblasts via Smad-dependent pathway. Therefore, HKL could be used as a potential agent for treating HPS and other fibrotic diseases.

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“…At the end of this phase, the myofibroblasts die by apoptosis leaving a rather acellular scar. However, multiple molecular and mechanical factors can affect wound healing after CL(P) surgery and promote fibrosis and scar formation resulting in major functional and aesthetic problems …”

Section: Cleft Surgery Can Results In Fibrosis and Scar Formationmentioning

confidence: 99%

Tissue engineering strategies combining molecular targets against inflammation and fibrosis, and umbilical cord blood stem cells to improve hampered muscle and skin regeneration following cleft repair

Schreurs

Suttorp

Mutsaers

et al. 2019

Medicinal Research Reviews

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Cleft lip with or without cleft palate is a congenital deformity that occurs in about 1 of 700 newborns, affecting the dentition, bone, skin, muscles and mucosa in the orofacial region. A cleft can give rise to problems with maxillofacial growth, dental development, speech, and eating, and can also cause hearing impairment. Surgical repair of the lip may lead to impaired regeneration of muscle and skin, fibrosis, and scar formation. This may result in hampered facial growth and dental development affecting oral function and lip and nose esthetics. Therefore, secondary surgery to correct the scar is often indicated. We will discuss the molecular and cellular pathways involved in facial and lip myogenesis, muscle anatomy in the normal and cleft lip, and complications following surgery. The aim of this review is to outline a novel molecular and cellular strategy to improve musculature and skin regeneration and to reduce scar formation following cleft repair. Orofacial clefting can be diagnosed in the fetus through prenatal ultrasound screening and allows planning for the harvesting of umbilical cord blood stem cells upon birth. Tissue engineering techniques using these cord blood stem cells and molecular targeting of inflammation and fibrosis during surgery may promote tissue regeneration. We expect that this novel strategy improves both muscle and skin regeneration, resulting in better function and esthetics after cleft repair.

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Growth factor pathways in hypertrophic scars: Molecular pathogenesis and therapeutic implications

Cited by 83 publications

References 102 publications

Current Therapeutic Approach to Hypertrophic Scars

Current Therapeutic Approach to Hypertrophic Scars

Honokiol Alleviates Hypertrophic Scar by Targeting Transforming Growth Factor-β/Smad2/3 Signaling Pathway

Tissue engineering strategies combining molecular targets against inflammation and fibrosis, and umbilical cord blood stem cells to improve hampered muscle and skin regeneration following cleft repair

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