Brimonidine reduces TGF-beta-induced extracellular matrix synthesis in human Tenon’s fibroblasts

Hong, Samin; Han, Sang-Sun; Kim, Chan Yun; Kim, Kang Yoon; Song, YoungGoo; Seong, Gong Je

doi:10.1186/s12886-015-0045-8

Cited by 15 publications

(6 citation statements)

References 17 publications

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“…Furthermore, we also identified that BRI induced significant inhibitory effects on the TGF-β2-related increases in the barrier function of 2D cells and the hardness of 3D spheroids. Similar to the BRI-induced inhibition of TGF-β2-related fibrosis in human Tenon’s fibroblasts in vitro [ 26 ], our results indicate that BRI causes TGF-β-stimulated ECM synthesis.…”

Section: Discussionsupporting

confidence: 82%

An α2-Adrenergic Agonist, Brimonidine, Beneficially Affects the TGF-β2-Treated Cellular Properties in an In Vitro Culture Model

et al. 2022

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We report herein on the effects of brimonidine (BRI), an α2-adrenergic agonist, on two-dimensional (2D) and three-dimensional (3D) cell-cultured TGF-β2-untreated and -treated human trabecular meshwork (HTM) cells. In the presence of TGF-β2 (5 ng/mL), (1) the effects of BRI on (1) the 2D HTM monolayers’ barrier function were investigated as estimated using trans-endothelial electrical resistance (TEER) measurement and FITC dextran permeability; (2) real-time analyses of cellular metabolism using a Seahorse Bioanalyzer; (3) the largeness and hardness of 3D spheroids; and (4) the expression of genes that encode extracellular matrix (ECM) proteins, including collagens (COL) 1, 4, and 6; fibronectin (FN) and α-smooth muscle actin (α-SMA); ECM modulators, including a tissue inhibitor of matrix proteinase (TIMP) 1–4; matrix metalloproteinase (MMP) 2, 9, and 14; and several endoplasmic reticulum (ER) stress-related genes, including the X-box-binding protein 1 (XBP1), the spliced XBP1 (sXBP1), glucose-regulated protein (GRP)78, GRP94, and CCAAT-enhancer-binding protein homologous protein (CHOP). BRI markedly inhibited the TGF-β2-induced increase in the values of TEER of the 2D cell monolayer and the hardness of the 3D spheroids, although it had no effect on their sizes. BRI also cancelled the TGF-β2-induced reduction in mitochondrial maximal respiration but had no effect on the glycolytic capacity. In addition, the gene expression of these molecules was quite different between the 2D and 3D cultures of HTM cells. The present observations found in this study indicate that BRI may beneficially affect TGF-β2-induced changes in both cultures, 2D and 3D, of HTM cells, although their structural and functional properties that were altered varied significantly between both cultures of HTM cells.

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Section: Discussionsupporting

confidence: 82%

An α2-Adrenergic Agonist, Brimonidine, Beneficially Affects the TGF-β2-Treated Cellular Properties in an In Vitro Culture Model

et al. 2022

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“…Myofibroblast formation is associated with fibrotic scars in various injury models 34 . TGF-β1 promotes IL-6 expression and induces trans-differentiation of human Tenon’s fibroblasts to myoblasts 35 . Therefore, we hypothesized that TGF-β1 also promotes IL-6 production in HCFs, inducing differentiation from cardiac fibroblasts to myofibroblasts.…”

Section: Resultsmentioning

confidence: 99%

Acute Hyperthermia Inhibits TGF-β1-induced Cardiac Fibroblast Activation via Suppression of Akt Signaling

Narikawa

Umemura

Tanaka

et al. 2018

Sci Rep

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Transforming growth factor-β1 (TGF-β1) induces phenotypic changes in fibroblasts to become myofibroblasts with increased production of extracellular matrix (ECM) components and cytokines. It is also known that excessive activation of myofibroblasts accelerates cardiac fibrosis, remodeling, and thus cardiac dysfunction. However, no effective therapy has been established to prevent this process although recent clinical studies have demonstrated the effectiveness of hyperthermia in cardiac dysfunction. The aim of this study was to examine the molecular mechanism of hyperthermia on TGF-β1-mediated phenotypic changes in cardiac fibroblasts. TGF-β1 increased the expression of IL-6, α-smooth muscle actin (α-SMA), and collagen in human cardiac fibroblasts (HCFs). Hyperthermia (42 °C) significantly prevented these changes, i.e., increases in IL-6, α-SMA, and collagen, as induced by TGF-β1 in a time-dependent manner. Immunoblotting showed that hyperthermia decreased Akt/S6K signaling, but did not affect Smad2 and Smad3 signaling. Pharmacological inhibition of Akt signaling mimicked these effects of hyperthermia. Furthermore, hyperthermia treatment prevented cardiac fibrosis in Ang II infusion mice model. Putting together, our findings suggest that hyperthermia directly inhibits TGF-β-mediated activation of HCFs via suppressing Akt/S6K signaling.

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“…Likewise, MSC transplanted into MPS VII mice cornea also acquired the characteristics of keratocytes. The transplanted cells supplied functional β-glucuronidase to degrade accumulated glycosaminoglycans thereby assisting in lysosome recycling ( 60 ). On the other hand, MSCs also secrete paracrine factors that exert anti-inflammation and anti-fibrosis functions, thus suppressing inflammatory neovascularization ( 61 , 62 ).…”

Section: Mscs For the Treatment Of Neonatal Eye Diseasesmentioning

confidence: 99%

The Potential of Mesenchymal Stromal Cell as Therapy in Neonatal Diseases

et al. 2020

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Mesenchymal stromal cells (MSCs) can be derived from various tissue sources, such as the bone marrow (BMSCs), adipose tissue (ADSCs), umbilical cord (UC-MSCs) and umbilical cord blood (UCB-MSCs). Clinical trials have been conducted to investigate the potential of MSCs in ameliorating neonatal diseases, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). In preclinical studies, MSC therapy has been tested for the treatment of various neonatal diseases affecting the heart, eye, gut, and brain as well as sepsis. Up to date, the number of clinical trials using MSCs to treat neonatal diseases is still limited. The data reported thus far positioned MSC therapy as safe with positive outcomes. However, most of these trials are still preliminary and generally smaller in scale. Larger trials with more appropriate controls and a longer follow-up period need to be conducted to prove the safety and efficacy of the therapy more conclusively. This review discusses the current application of MSCs in treating neonatal diseases, its mechanism of action and future direction of this novel therapy, including the potential of using MSC-derived extracellular vesicles instead of the cells to treat various clinical conditions in the newborn.

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Brimonidine reduces TGF-beta-induced extracellular matrix synthesis in human Tenon’s fibroblasts

Cited by 15 publications

References 17 publications

An α2-Adrenergic Agonist, Brimonidine, Beneficially Affects the TGF-β2-Treated Cellular Properties in an In Vitro Culture Model

An α2-Adrenergic Agonist, Brimonidine, Beneficially Affects the TGF-β2-Treated Cellular Properties in an In Vitro Culture Model

Acute Hyperthermia Inhibits TGF-β1-induced Cardiac Fibroblast Activation via Suppression of Akt Signaling

The Potential of Mesenchymal Stromal Cell as Therapy in Neonatal Diseases

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