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首页> 外文期刊>BMC Ophthalmology >UVB-mediated down-regulation of proteasome in cultured human primary pterygium fibroblasts
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UVB-mediated down-regulation of proteasome in cultured human primary pterygium fibroblasts

机译：UVB介导的培养人原发性翼状胬肉成纤维细胞中蛋白酶的下调

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Pterygium is a condition characterized by epithelial overgrowth of the cornea, inflammatory cell infiltration and an abnormal extracellular matrix accumulation. Chronic UV exposure is considered as a pathogenic factor of this disease. Proteasome is an intracellular multi-subunit protease complex that degrades intracellular proteins. Among proteasome subunits the β5 (PSMB5), bearing chymotrypsin-like activity. It is considered as the main proteasome subunit and its expression is mediated by Nrf2-ARE pathway in many cell types. This study investigates the expression of PSMB5 in pterygium and the effect of UVB irradiation on its expression and activity in pterygium fibroblasts. Normal conjunctival and pterygium specimens were obtained from the bulbar conjunctiva of patients undergoing cataract surgery and from patients with pterygium undergoing surgical removal of primary tissue, respectively. Fibroblasts were isolated upon treatment of specimens with clostridium collagenase. The expression of PSMB5 and Nrf2 in tissues and cells was ascertained by RT-PCR analysis and western blotting. Cell survival was measured by the MTT method and the proteasome chymotrypsin-like activity was determined by fluorometry. RT-PCR analysis showed that the expression of PSMB5 was significantly lower in pterygium than in normal conjunctiva. The expression of PSMB5 was mediated by the Nrf2/ARE pathway as indicated by using the Nrf2 activator Oltipraz. The expression of PSMB5 and Nrf2 by pterygium fibroblasts was suppressed in a dose dependent manner following UVB radiation of 0-50?mJ/cm2 doses. The expression of PSMB5, but not of Nrf2, remained at almost the control levels, when UVB exposure was performed after pre-incubation of cells with the src kinases inhibitor PP2. UVB irradiation had very low deleterious effect on fibroblasts survival, while it did not affect the proteasome chymotrypsin-like activity. In pterygium fibroblasts, UVB exposure leads to down-regulation of Nrf2/ARE-mediated PSMB5 gene expression, in which src kinases may be implicated. This effect may be partially responsible for the lower expression of PSMB5 detected in pterygium as compared to normal conjunctiva.
机译：翼状胬肉是角膜，炎症细胞浸润和异常细胞外基质累积的上皮过度生长的一种病症。慢性紫外线暴露被认为是这种疾病的致病因子。蛋白酶体是细胞内多亚基蛋白酶复合物，其降解细胞内蛋白质。在蛋白酶体亚基中，β5（PSMB5），携带胰凝乳蛋白酶样活性。它被认为是主要的蛋白酶体亚基，其表达由NRF2介导 - 是许多细胞类型中的途径。本研究研究了PSMB5在翼状胬肉中的表达及UVB辐射对翼状胬肉细胞表达和活性的影响。从经历白内障手术的患者的鳞片结膜和牙根患者分别从接受手术移除初级组织的患者的患者的脉冲结膜中获得正常结膜和翼状胬肉标本。用梭菌胶原酶处理试样后分离成纤维细胞。通过RT-PCR分析和蛋白质印迹确定PSMB5和NRF2中的表达和细胞中的表达。通过MTT方法测量细胞存活，并通过荧光测定法测定蛋白酶体胰蛋白酶样活性。 RT-PCR分析表明，PermB5的表达在翼状胬肉中显着低于正常结膜。如通过使用NRF2活化剂OLTIPRAZ所示，由NRF2 /是途径介导的PSMB5的表达。在UVB辐射的0-50μm/ cm2剂量之后，以剂量依赖性方式抑制PSMB5和NRF2的表达。当通过SRC激酶抑制剂PP2预孵育细胞后，在对照水平几乎进行PSMB5但不具有NRF2的表达。 UVB辐射对成纤维细胞存活具有非常低的有害影响，而它不会影响蛋白酶体胰蛋白酶样活性。在翼状胬肉成纤维细胞中，UVB暴露导致NRF2 /介导的PSMB5基因表达的下调，其中可以涉及SRC激酶。与正常结膜相比，该效果可以部分地负责翼状胬肉中检测到的PSMB5的较低表达。

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