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首页> 外文期刊>Journal of Cellular Physiology >Regulation of plasticity and fibrogenic activity of trabecular meshwork cells by rho GTPase signaling
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Regulation of plasticity and fibrogenic activity of trabecular meshwork cells by rho GTPase signaling

机译：监管的可塑性和纤维发生的活动ρGTPase的小梁网细胞信号

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Glaucoma, a prevalent blinding disease is commonly associated with increased intraocular pressure due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM). Although increased TM tissue contraction and stiffness in association with accumulation of extracellular matrix (ECM) are believed to be partly responsible for increased resistance to AH outflow, the extracellular cues and intracellular mechanisms regulating TM cell contraction and ECM production are not well defined. This study tested the hypothesis that sustained activation of Rho GTPase signaling induced by lysophosphatidic acid (LPA), TGF-β, and connective tissue growth factor (CTGF) influences TM cell plasticity and fibrogenic activity which may eventually impact resistance to AH outflow. Various experiments performed using human TM cells revealed that constitutively active RhoA (RhoAV14), TGF-β2, LPA, and CTGF significantly increase the levels and expression of Fibroblast Specific Protein-1 (FSP-1), α-smooth muscle actin (αSMA), collagen-1A1 and secretory total collagen, as determined by q-RT-PCR, immunofluorescence, immunoblot, flow cytometry and the Sircol assay. Significantly, these changes appear to be mediated by Serum Response Factor (SRF), myocardin-related transcription factor (MRTF-A), Slug, and Twist-1, which are transcriptional regulators known to control cell plasticity, myofibroblast generation/activation and fibrogenic activity. Additionally, the Rho kinase inhibitor-Y27632 and anti-fibrotic agent-pirfenidone were both found to suppress the TGF-β2-induced expression of αSMA, FSP-1, and collagen-1A1. Taken together, these observations demonstrate the significance of RhoA/Rho kinase signaling in regulation of TM cell plasticity, fibrogenic activity, and myofibroblast activation, events with potential implications for the pathobiology of elevated intraocular pressure in glaucoma patients. J. Cell. Physiol. 229: 927-942, 2014.
机译：青光眼,普遍致盲疾病是常见的与眼压增高有关由于受损的房水引流(啊)通过小梁网(TM)。增加小梁网组织的收缩和僵硬与细胞外的积累矩阵(ECM)被认为是部分负责增加抵抗啊流出,细胞外信号和细胞内TM细胞收缩和ECM的调节机制生产不是很好。测试持续激活的假设ρGTPase信号引起的lysophosphatidic酸(LPA)、TGF -β,结缔组织生长因子(CTGF)的影响TM细胞可塑性和纤维发生的活动最终可能影响抗啊流出。各种实验使用人类TM执行细胞RhoA透露,持续活跃(RhoAV14), TGF -β2,LPA, CTGF显著增加纤维母细胞的水平和表达特定蛋白1 (FSP-1),α平滑肌肉肌动蛋白(αSMA)、collagen-1A1和分泌由q-RT-PCR胶原蛋白,免疫荧光、免疫印迹、流式细胞术和Sircol化验。变化似乎是由血清反应myocardin-related转录因子(SRF)因子(MRTF-A)、蛞蝓和Twist-1转录监管机构控制细胞可塑性,myofibroblast代/激活和纤维发生的活动。激酶inhibitor-Y27632和anti-fibroticagent-pirfenidone都发现抑制TGF -βαSMA 2-induced表达式,FSP-1,collagen-1A1。演示的重要性RhoA /ρ激酶信号调节TM细胞可塑性,纤维发生的活动和myofibroblast激活、事件与潜在影响病理学的升高眼内青光眼患者的压力。229: 927-942, 2014.

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