siRNA Knockdown of Tissue Inhibitor of Metalloproteinase-1 in Keloid Fibroblasts Leads to Degradation of Collagen Type I

Aoki, Masayoshi; Miyake, Keisuke; Ogawa, Rei; Dohi, Teruyuki; Akaishi, Satoshi; Hyakusoku, Hiko; Shimada, Takashi

doi:10.1038/jid.2013.396

Cited by 68 publications

(51 citation statements)

References 44 publications

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“…However, some research has found that the expression of TIMP-1 is significantly higher in the scar tissue of patients with HS than in scar tissues of patients with normotrophic scars 32 . Moreover, targeting TIMP-1 using small interfering RNA has significant therapeutic potential as an approach to treating keloids 33 . In this study, the expression of TIMP-1 was significantly decreased with Endostar treatments, while the group that did not receive Endostar therapy showed over expression of TIMP-1.…”

Section: Discussionmentioning

confidence: 99%

Recombinant human endostatin reduces hypertrophic scar formation in rabbit ear model through down-regulation of VEGF and TIMP-1

2016

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Background: Recombinant human endostatin (Endostar) has been widely used to suppress angiogenesis in carcinoma patients. Hypertrophic scar (HS) tissue, much like a carcinoma, is often associated with angiogenesis. However, there have been few studies conducted on the effects of Endostar on HS or its mechanism. Objective: This paper investigated the effects Endostar on the HS of rabbit ears and studied the effects of Endostar on VEGF and TIMP-1 expression. Methods: Sixteen New Zealand white rabbits were used to establish HS models. Then, rabbit ears containing HS were randomly assigned to either the Endostar group or the control group. The changes of appearance and histology were evaluated using the naked eye, hematoxylin eosin staining, and a scar elevation index. The VEGF and TIMP-1 expressions were detected by immunohistochemical staining, RT-PCR, and western blot. Results: The thickness of the connective tissue in the Endostar group were thinner, the numbers of micro vessels and fibroblasts were fewer, and the collagen fibers were smoother. Moreover, the mRNA and protein expressions of VEGF and TIMP-1 in the Endostar group were significantly lower than those in the control group. Conclusion:The results suggested that Endostar reduced the formation of HS by down-regulation of VEGF and TIMP-1 expressions.

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Section: Discussionmentioning

confidence: 99%

Recombinant human endostatin reduces hypertrophic scar formation in rabbit ear model through down-regulation of VEGF and TIMP-1

2016

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“…Metaloproteinazy macierzy pozakomórkowej i ich substraty [39][40][41] TIMP-2, TIMP-3, TIMP-4) i niespecyficznych inhibitorów (α2-makroglobuliny, α1-antytrypsyny, inhibitora plazminogenu 1) [45][46][47][48][49][50][51][52][53][54]. Szczególne znaczenie w formowaniu keloidów mają kolagenaza 1 (MMP-1) i żelatynazy (MMP-2 i MMP-9).…”

Section: Czynnik Wzrostu Tkanki łąCznejunclassified

Review papers Some molecular aspects of the fibroproliferative process in keloids

Antończak¹,

Jurzak²,

Adamczyk³

et al. 2015

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StreSzczenieProcesy naprawcze (reperatywne) uszkodzonych tkanek należą do podstawowych procesów biologicznych zapewniających utrzymanie homeostazy organizmu. Zasadniczo obejmują fazę zapalną, proliferacyjną oraz przebudowy. Końcowym efektem gojenia się uszkodzonych tkanek jest powstanie blizny. Nieprawidłowości w przebiegu gojenia się ran mogą być przyczyną tworzenia keloidów (bliznowców). W patofizjologii keloidów obserwuje się zarówno nieprawidłowości w migracji, proliferacji i apoptozie komórek, jak i w syntezie oraz sekrecji białek, cytokin, enzymów proteolitycznych degradujących składniki macierzy pozakomórkowej, a także ich inhibitorów. Dotychczasowo stosowane terapie nie przynoszą zadowalających efektów kosmetycznych. Obecnie prowadzone badania skupiają się na poszukiwaniu metod bezpośredniego hamowania procesu fibroproliferacyjnego poprzez modulowanie ekspresji cytokin, hamowanie proliferacji fibroblastów oraz regulowanie biosyntezy i degradacji składników macierzy pozakomórkowej. AbStrActReparation of damaged tissues is an essential biological process that ensures maintenance of homeostasis. Basically it includes phases of inflammation, proliferation and remodeling. The result of healing of damaged tissues is scar formation. Abnormalities in the course of wound healing may lead to keloid formation. The pathophysiology of keloids is characterized by improper migration, proliferation and apoptosis of cells as well as imbalanced synthesis and secretion of proteins, cytokines, proteolytic enzymes and their inhibitors. To date, applied therapeutic methods do not lead to satisfactory cosmetic results of the treatment. Current research focuses on developing methods for direct inhibition of the fibroproliferative process, mainly through modulation of cytokine expression and in consequence suppression of fibroblast proliferation and balancing of synthesis and degradation of extracellular matrix components.

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“…Histological studies revealed that keloid contains overabundant fibroblasts undergoing mitotic division, in which excessive collagen deposition and myxoid stroma can be observed [4]. The etiology of keloid has remarkable similarity with that of tumor, which is often driven by abnormally overexpression of oncogenes, resulting in uncontrolled growth of cells [5][6][7][8]. Indeed, therapies developed to treat keloid such as interferon therapy, intralesional administration of 5-fluorouracil and tamoxifen, excision, and radiation therapy [9][10][11], were originated from cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Inhibits Proliferation and Promotes Apoptosis of Keloid Fibroblasts by Targeting HIF-1α

Si¹,

Qin²,

Xiao³

et al. 2017

J Clin Exp Dermatol Res

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Keloid is characterized by red, tickling, hard and irregular raised tissues, and tends to outgrow its origin. It occurs frequently in young adults and appears as refractory to prevailing therapies. Although histological studies have revealed striking similarities of keloids with cancer, such as uncontrolled cell growth, and many of the therapies in clinical practice including -fluorouracil and tamoxifen, excision, and radiation therapy were borrowed from cancer management, the etiology of keloid has remained to be explored to provide insights for developing effective therapeutic modalities. Hypoxic stress around tumors was frequently reported as conferring growth momentum to tumor cells. The hypoxia caused by fast growing of keloid fibroblasts may also be a risk factor that antagonizes therapies. Resveratrol has received intense attention in cancer researches since its anti-proliferative effect on human pulmonary artery smooth muscle cells were revealed. In this study, we first revealed that hypoxia promotes proliferation and inhibit apoptosis of keloid fibroblasts, which highlights the potential obstacle in treating keloids. Further, we demonstrated resveratrol could reverse the effect of hypoxia on keloids, which involves down-regulation of HIF-1α. Moreover, the collagen synthesis of keloid fibroblasts was also inhibited by resveratrol, which was corresponding with HIF-1α suppression. These results provide complementary evidence to the multiple molecular signalings controlled by resveratrol and suggest a pathway implicates resveratrol to regulate expression of procollagen expression via HIF-1α.

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siRNA Knockdown of Tissue Inhibitor of Metalloproteinase-1 in Keloid Fibroblasts Leads to Degradation of Collagen Type I

Cited by 68 publications

References 44 publications

Recombinant human endostatin reduces hypertrophic scar formation in rabbit ear model through down-regulation of VEGF and TIMP-1

Recombinant human endostatin reduces hypertrophic scar formation in rabbit ear model through down-regulation of VEGF and TIMP-1

Review papers Some molecular aspects of the fibroproliferative process in keloids

Resveratrol Inhibits Proliferation and Promotes Apoptosis of Keloid Fibroblasts by Targeting HIF-1α

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