A Novel Aptamer Targeting TGF-β Receptor II Inhibits Transdifferentiation of Human Tenon's Fibroblasts into Myofibroblast

Zhu, Xiaoyan; Li, Lei; Zou, Lingyun; Zhu, Xudong; Xian, Guangjun; Li, Haijun; Tan, Yan; Xie, Lin

doi:10.1167/iovs.12-10198

Cited by 25 publications

(18 citation statements)

References 30 publications

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“…Contraction of a collagen gel mediated by human Tenon's capsule fibroblasts (HTFs) has thus been studied as a model of subconjunctival wound healing 3. The cytokine transforming growth factor β (TGF-β) is a key mediator of wound healing and tissue repair.…”

Section: Introductionmentioning

confidence: 99%

All-trans-retinoic acid inhibition of transforming growth factor-β-induced collagen gel contraction mediated by human Tenon fibroblasts: role of matrix metalloproteinases

et al. 2015

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Section: Introductionmentioning

confidence: 99%

All-trans-retinoic acid inhibition of transforming growth factor-β-induced collagen gel contraction mediated by human Tenon fibroblasts: role of matrix metalloproteinases

et al. 2015

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“…Neither of the two peptides could bind to e.g., BMPR–IA (Alk3), ActRII (which also binds BMPs) and the co-receptors β-glycan and endoglin [78]. More recently, aptamers were raised (using SELEX) against the extracellular domain of TβRII and used in vitro to investigate the TGFβ-induced myofibroblast transdifferentiation of human Tenon’s fibroblasts [79]. In particular, the aptamer S58 was found to antagonize the effects of TGFβ2 on differentiation, as the aptamer interferes with activation and nuclear translocation of Smad2.…”

Section: Aptamers and Their Use In Targeting Of Signal Transductiomentioning

confidence: 99%

“…In particular, the aptamer S58 was found to antagonize the effects of TGFβ2 on differentiation, as the aptamer interferes with activation and nuclear translocation of Smad2. Transdifferentiated myofibroblasts show increased contractile activity associated with de novo expression of α-Smooth Muslce Actin (α-SMA), which is downregulated by S58 [79]. …”

Section: Aptamers and Their Use In Targeting Of Signal Transductiomentioning

confidence: 99%

Aptamers and Their Potential to Selectively Target Aspects of EGF, Wnt/β-Catenin and TGFβ–Smad Family Signaling

Conidi

Berghe

Huylebroeck

2013

IJMS

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The smooth identification and low-cost production of highly specific agents that interfere with signaling cascades by targeting an active domain in surface receptors, cytoplasmic and nuclear effector proteins, remain important challenges in biomedical research. We propose that peptide aptamers can provide a very useful and new alternative for interfering with protein–protein interactions in intracellular signal transduction cascades, including those emanating from activated receptors for growth factors. By their targeting of short, linear motif type of interactions, peptide aptamers have joined nucleic acid aptamers for use in signaling studies because of their ease of production, their stability, their high specificity and affinity for individual target proteins, and their use in high-throughput screening protocols. Furthermore, they are entering clinical trials for treatment of several complex, pathological conditions. Here, we present a brief survey of the use of aptamers in signaling pathways, in particular of polypeptide growth factors, starting with the published as well as potential applications of aptamers targeting Epidermal Growth Factor Receptor signaling. We then discuss the opportunities for using aptamers in other complex pathways, including Wnt/β-catenin, and focus on Transforming Growth Factor-β/Smad family signaling.

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“…The TGF-β family is the main stimulator leading to conjunctival scarring post trabeculectomy, and various cells, such as fibroblasts and macrophages, can secrete them [15]. It was previously reported that TGF-β2 could increase α-smooth muscle actin (α-SMA) expression and the transdifferentiation of fibroblasts in conjunctiva to myofibroblasts [16]. In another previous study, the authors’ findings revealed that bleb failure post trabeculectomy primarily occurred due to the excessive accumulation of collagen in the subconjunctival space, and that high activity of TGF-β was associated with scarring [17].…”

Section: Introductionmentioning

confidence: 99%

Effects of Gelatin Hydrogel Containing Anti-Transforming Growth Factor-β Antibody in a Canine Filtration Surgery Model

Maeda

Kojima

Sugiyama

et al. 2017

IJMS

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In this present study, we investigated the effect of a controlled release of anti-transforming growth factor β (TGF-β) antibody on intraocular pressure (IOP), bleb formation, and conjunctival scarring in a canine glaucoma filtration surgery model using gelatin hydrogel (GH). Glaucoma surgery models were made in 14 eyes of 14 beagles and divided into the following two groups: (1) subconjunctival implantation of anti-TGF-β antibody-loaded GH (GH-TGF-β group, n = 7), and (2) subconjunctival implantation of GH alone (GH group, n = 7). IOP and bleb features were then assessed in each eye at 2- and 4-weeks postoperative, followed by histological evaluation. We found that IOP was significantly reduced at 4-weeks postoperative in the two groups (p < 0.05) and that IOP in the GH-TGF-β-group eyes was significantly lower than that in the GH-group eyes (p = 0.006). In addition, the bleb score at 4-weeks postoperative was significantly higher in the GH-TGF-β group than in the GH group (p < 0.05), and the densities of fibroblasts, proliferative-cell nuclear antigen (PCNA)-positive cells, mast cells, and TGF-β-positive cells were significantly lower in the GH-TGF-β group than in the GH group. The findings of this study suggest that, compared with the GH-group eyes, implantation of anti-TGF-β antibody-loaded GH maintains IOP reduction and bleb formation by suppressing conjunctival scarring due to the proliferation of fibroblasts for a longer time period via a sustained release of anti-TGF-β antibody from GH.

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A Novel Aptamer Targeting TGF-β Receptor II Inhibits Transdifferentiation of Human Tenon's Fibroblasts into Myofibroblast

Abstract: Our study revealed that a novel aptamer binding TβRII inhibited TGF-β2-induced myofibroblast transdifferentiation in HTFs.

Cited by 25 publications

References 30 publications

All-trans-retinoic acid inhibition of transforming growth factor-β-induced collagen gel contraction mediated by human Tenon fibroblasts: role of matrix metalloproteinases

All-trans-retinoic acid inhibition of transforming growth factor-β-induced collagen gel contraction mediated by human Tenon fibroblasts: role of matrix metalloproteinases

Aptamers and Their Potential to Selectively Target Aspects of EGF, Wnt/β-Catenin and TGFβ–Smad Family Signaling

Effects of Gelatin Hydrogel Containing Anti-Transforming Growth Factor-β Antibody in a Canine Filtration Surgery Model

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