Isoform-selective upregulation of mast cell chymase in the development of skin fibrosis in scleroderma model mice.
Isoform-selective upregulation of mast cell chymase in the development of skin fibrosis in scleroderma model mice.
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硬皮病模型小鼠皮肤纤维化发展过程中肥大细胞糜酶的亚型选择性上调。
DOI：
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发表时间：
2001
影响因子：
6.5
通讯作者：
Hideki Okunishi
中科院分区：
文献类型：
--
作者：
E. Kakizoe;Naotaka Shiota;Yoko Tanabe;K. Shimoura;Yuta Kobayashi;Hideki Okunishi
结缔组织型肥大细胞和糜酶（一种其分泌颗粒特有的蛋白酶）的参与与纤维化疾病有关。为了阐明糜酶在纤维增生性炎症中的作用，在这项研究中，我们研究了糜酶的酶活性和mRNA表达的紧皮肤小鼠的皮肤;同基因的苍白小鼠作为对照。背侧皮肤标本，年龄为5，10和20周的小鼠进行了评价，形态和生化分析。在10和20周龄时，紧皮真皮中羟脯氨酸浓度高于苍白。在任何年龄，皮下纤维层厚的皮肤紧比苍白。根据这些纤维的变化，结缔组织型肥大细胞计数和糜酶活性较高，在皮肤紧张的皮肤比在苍白的皮肤长达20周的年龄。通过竞争性逆转录酶聚合酶链反应技术，定量测定了与之匹配的（10周龄）紧皮和苍白的结缔组织型肥大细胞特异性糜酶（小鼠肥大细胞蛋白酶-4）的mRNA，结果显示紧皮中的水平高于苍白。相比之下，小鼠肥大细胞蛋白酶-5的mRNA水平，未分化的肥大细胞的糜蛋白酶亚型，在紧皮肤的皮肤只有十分之一的小鼠肥大细胞蛋白酶-4和没有不同的小鼠肥大细胞蛋白酶-5的mRNA水平苍白小鼠。一项原位杂交研究证实，小鼠肥大细胞蛋白酶-4的结缔组织型肥大细胞在紧张的皮肤比苍白的皮肤更高的表达。这些结果有力地支持了结缔组织型肥大细胞糜酶在皮肤纤维增生性重塑中起着至关重要的作用的论点。
The involvement of connective-tissue-type mast cells and chymase, a protease unique to their secretory granules, has been implicated in fibrotic diseases. To elucidate the role of chymase in fibroproliferative inflammation, in this study we examined the enzymatic activity and mRNA expression of chymase in the sclerotic skin of tight-skin mice; syngeneic Pallid mice served as the control. Dorsal skin specimens from mice aged 5, 10, and 20 wk were evaluated by morphometric and biochemical analyses. At ages 10 and 20 wk, the hydroxyproline concentration in tight-skin dermis was higher than that in Pallid. At any age, the subcutaneous fibrous layer was thicker in tight-skin than in Pallid. In accordance with these fibrous changes, both connective-tissue-type mast cell counts and chymase activity were higher in tight-skin skin than in Pallid skin up to 20 wk of age. Age-matched (10-wk-old) tight-skin and Pallid were quantified for their mRNA of connective-tissue-type mast-cell-specific chymase, mouse mast cell protease-4, by the competitive reverse transcriptase polymerase chain reaction technique, which revealed its higher level in tight-skin than Pallid. In contrast, the mRNA level of mouse mast cell protease-5, the chymase isoform of undifferentiated mast cells, in tight-skin skin was only a tenth that of mouse mast cell protease-4 and no different from the mouse mast cell protease-5 mRNA level of Pallid mice. An in situ hybridization study confirmed the higher expression of mouse mast cell protease-4 by connective-tissue-type mast cells in tight-skin skin than Pallid skin. These results strongly support the contention that the connective-tissue-type mast cell chymase plays a crucial role in fibroproliferative remodeling of the skin.
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影响因子：
4.4
作者：
G. Sempowski;M. Beckmann;Stephen Derdak;R. Phipps
通讯作者：
G. Sempowski;M. Beckmann;Stephen Derdak;R. Phipps
具有结缔组织和类似于人类系统性硬化症的自身免疫特征的（紧皮肤/NZB）F1 杂交小鼠的免疫学特征。
影响因子：
12.8
作者：
Bocchieri,MH;Christner,PJ;Henriksen,PD;Jimenez,SA
通讯作者：
Jimenez,SA
白细胞介素 10 和白细胞介素 3 对粘膜肥大细胞特异性蛋白酶基因 MMCP-2 的转录调节。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ghildyal,N;McNeil,HP;Gurish,MF;Austen,KF;Stevens,RL
通讯作者：
Stevens,RL
皮肤紧实的小鼠是硬皮病的实验模型。
影响因子：
5
作者：
Kasturi,KN;Shibata,S;Muryoi,T;Bona,CA
通讯作者：
Bona,CA