Induction by Latanoprost of Collagen Gel Contraction Mediated by Human Tenon Fibroblasts: Role of Intracellular Signaling Molecules

Liu, Yang; Ko, Ji‐Ae; Yanai, Ryoji; Kimura, Kazuhiro; Chikama, Tai-ichiro; Sagara, Takeshi; Nishida, Teruo

doi:10.1167/iovs.07-0451

Cited by 27 publications

(36 citation statements)

References 45 publications

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“…It has been reported that MAPK inhibitors (JNK, ERK, or p38 inhibitors) inhibit gel contraction mediated by fibroblasts [29,30,31]. In the current study, we investigated the role of MAPKs in regulating endothelial cell-mediated collagen gel contraction in response to TNF-α stimulation.…”

Section: Discussionmentioning

confidence: 96%

Differential Roles of JNK, ERK1/2, and p38 Mitogen-Activated Protein Kinases on Endothelial Cell Tissue Repair Functions in Response to Tumor Necrosis Factor-α

et al. 2012

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Tumor necrosis factor (TNF)-α can alter tissue repair functions in a variety of cells including endothelial cells. However, the mechanism by which TNF-α mediates these functional changes has not fully been studied. We investigated the role of mitogen-activated protein kinases (MAPKs) on mediating the regulatory effect of TNF-α on the tissue repair functions of human pulmonary artery endothelial cells (HPAECs). TNF-α protected HPAECs from undergoing apoptosis induced by serum and growth factor deprivation, augmented collagen gel contraction, and stimulated wound closure. TNF-α activated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38. Inhibitors of JNK (SP600125, 5 µm) or ERK1/2 (PD98059, 5 µm) significantly inhibited TNF-α-stimulated cell survival, contraction of collagen gels, and wound closure. In contrast, the p38 inhibitor SB203580 (5 µm) further amplified all of the TNF-α effects on HPAECs. TNF-α specifically activated p38α but not other p38 isoforms and suppression of p38α by an siRNA resulted in further amplification of the TNF-α effect. These results suggest that TNF-α stimulates tissue repair functions of HPAECs, and this may be mediated, at least in part, positively via JNK and ERK1/2, and negatively through p38α. MAPKs may play a role in endothelial cell-mediated tissue repair, especially in an inflammatory milieu where TNF-α is present.

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Section: Discussionmentioning

confidence: 96%

Differential Roles of JNK, ERK1/2, and p38 Mitogen-Activated Protein Kinases on Endothelial Cell Tissue Repair Functions in Response to Tumor Necrosis Factor-α

et al. 2012

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“…Interestingly, these results are in accordance with a previous report on HTF cells showing that latanoprost-induced HTF CPCG contraction was dependent on p38 activation but also seemed mediated by ERK and c-Jun Nterminal kinase signaling. 53 In another study, p38 inhibition blocked TGF-b-mediated HTF CPCG contraction and myofibroblast transition while ERK signaling inhibition, by U0126, induced a spontaneous contraction of HTF CPCG. 52 Hence, we extended these observations made on HTF to TM cells and showed that latanoprost induced the generation of contractile forces in TM cells, a characteristic of myofibroblast phenotype, through ROCK and p38 activation.…”

Section: Discussionmentioning

confidence: 96%

“…Other studies using CPCG as a force-sensing device showed that latanoprost induced contraction of human Tenon fibroblasts (HTF) from the conjunctiva and correlated with the formation of actin stress fibers, consistent with our observations. 53 In contrast, endothelin-dependent short-time contraction of bovine TM strips has been reported to be inhibited by FP receptor agonists, suggesting that the FP receptor activation could potentially lead to opposite effects at shorter time points. 54 Finally, EP2 receptor activation decreased CPCG contraction by dermal fibroblasts.…”

Section: Discussionmentioning

confidence: 98%

Activation of Prostaglandin FP and EP2 Receptors Differently Modulates Myofibroblast Transition in a Model of Adult Primary Human Trabecular Meshwork Cells

Kalouche

Béguier

Bakria

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Prostaglandin F2a analogues are the first-line medication for the treatment of ocular hypertension (OHT), and prostanoid EP2 receptor agonists are under clinical development for this indication. The goal of this study was to investigate the effects of F prostanoid (FP) and EP2 receptor activation on the myofibroblast transition of primary trabecular meshwork (TM) cells, which could be a causal mechanism of TM dysfunction in glaucoma.METHODS. Human primary TM cells were treated with either latanoprost or butaprost and TGFb2. Trabecular meshwork contraction was measured in a three-dimensional (3D) TM cellpopulated collagen gel (CPCG) model. Expression of a-smooth muscle actin (a-SMA) and phosphorylation of myosin light chain (MLC) were determined by Western blot. Assembly of actin stress fibers and collagen deposition were evaluated by immunocytochemistry. Involvement of p38, extracellular signal-regulated kinase (ERK), and Rho-associated kinase (ROCK) pathways as well as matrix metalloproteinase activation was tested with specific inhibitors.RESULTS. In one source of validated adult TM cells, latanoprost induced cell contraction as observed by CPCG surface reduction and increased actin polymerization, a-SMA expression, and MLC phosphorylation, whereas butaprost inhibited TGF-b2-induced CPCG contraction, actin polymerization, and MLC phosphorylation. Both agonists inhibited TGF-b2-dependent collagen deposition. The latanoprost effects were mediated by p38 pathway.CONCLUSIONS. Latanoprost decreased TM collagen accumulation but promoted a contractile phenotype in a source of adult TM cells that could modulate the conventional outflow pathway. In contrast, butaprost attenuated both TM contraction and collagen deposition induced by TGF-b2, thereby inhibiting myofibroblast transition of TM cells. These results open new perspectives for the management of OHT.

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“…The cells from each patient were cultured separately in MEM supplemented with 10% FBS, and they were used for the present study after 3 to 7 passages. 10 Assay of IL-6, IL-8, and MCP-1 Release Assays were performed as described previously. 12 HTFs were cultured in 24-well plates until they achieved confluence, after which the culture medium was replaced with serum-free MEM for 1 day.…”

Section: Isolation and Culture Of Htfsmentioning

confidence: 99%

“…7 Various studies have investigated the effects of antiglaucoma drugs on Tenon's capsule fibroblasts, [8][9][10] which contribute to the inflammatory response in the conjunctiva and to wound healing after glaucoma filtration surgery. We previously showed that latanoprost induced collagen gel contraction mediated by Tenon's capsule fibroblasts 10 or corneal fibroblasts.…”

mentioning

confidence: 99%

Latanoprost-induced Cytokine and Chemokine Release From Human Tenon’s Capsule Fibroblasts

Liu¹,

Liu

et al. 2015

Journal of Glaucoma

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Induction by Latanoprost of Collagen Gel Contraction Mediated by Human Tenon Fibroblasts: Role of Intracellular Signaling Molecules

Cited by 27 publications

References 45 publications

Differential Roles of JNK, ERK1/2, and p38 Mitogen-Activated Protein Kinases on Endothelial Cell Tissue Repair Functions in Response to Tumor Necrosis Factor-α

Differential Roles of JNK, ERK1/2, and p38 Mitogen-Activated Protein Kinases on Endothelial Cell Tissue Repair Functions in Response to Tumor Necrosis Factor-α

Activation of Prostaglandin FP and EP2 Receptors Differently Modulates Myofibroblast Transition in a Model of Adult Primary Human Trabecular Meshwork Cells

Latanoprost-induced Cytokine and Chemokine Release From Human Tenon’s Capsule Fibroblasts

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