Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues
Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues
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血管紧张素 II 通过调节糖尿病皮肤组织中金属蛋白酶-1 的组织抑制剂来调节胶原代谢
DOI：
10.1177/1479164113485461
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发表时间：
2013-09-01
影响因子：
2.4
通讯作者：
Yan, Li
中科院分区：
文献类型：
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作者：
Ren, Meng;Hao, Shaoyun;Yan, Li
本研究探讨血管紧张素II（Ang II）对糖尿病皮肤胶原代谢调节中基质金属蛋白酶-1（MMP-1）/组织金属蛋白酶抑制剂-1（TIMP-1）平衡的影响。收集糖尿病模型皮肤组织，原代培养成纤维细胞，在Ang Ⅱ处理前用Ang Ⅱ受体抑制剂处理。用组织化学方法测定I型胶原（科尔I）和III型胶原（科尔III）。采用聚合酶链反应（PCR）、Western blot或酶联免疫吸附试验（ELISA）检测皮肤组织和成纤维细胞中转化生长因子-β（TGF-β）、基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶组织抑制剂-1（TIMP-1）及Ⅰ型和Ⅲ型前胶原前肽的表达。与对照组相比，注射链脲佐菌素（STZ）的小鼠胶原蛋白I/III比值的变化记录了胶原蛋白功能障碍。这伴随着糖尿病皮肤组织中TGF-β、TIMP-1和I型和III型前胶原前肽的表达增加。在原代培养的成纤维细胞中，Ang II促进胶原合成，同时伴有TGF-β、TIMP-1和I型和III型前胶原表达的增加，并且这些增加被Ang II 1型（AT 1）受体阻断剂氯沙坦抑制，但不受Ang II 2型（AT 2）受体拮抗剂PD 123319的影响。这些发现提供了证据，表明Ang-II介导的MMP-1和TIMP-1产生的变化通过AT 1受体和TGF-β依赖性机制发生。
We investigated the effect of angiotensin II (Ang II) on matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) balance in regulating collagen metabolism of diabetic skin. Skin tissues from diabetic model were collected, and the primary cultured fibroblasts were treated with Ang II receptor inhibitors before Ang II treatment. The collagen type I (Coll I) and collagen type III (Coll III) were measured by histochemistry. The expressions of transforming growth factor-β (TGF-β), MMP-1, TIMP-1 and propeptides of types I and III procollagens in skin tissues and fibroblasts were quantified using polymerase chain reaction (PCR), Western blot or enzyme-linked immunosorbent assay (ELISA). Collagen dysfunction was documented by changed collagen I/III ratio in streptozotocin (STZ)-injected mice compared with controls. This was accompanied by increased expression of TGF-β, TIMP-1 and propeptides of types I and III procollagens in diabetic skin tissues. In primary cultured fibroblasts, Ang II prompted collagen synthesis accompanied by increases in the expressions of TGF-β, TIMP-1 and types I and III procollagens, and these increases were inhibited by losartan, an Ang II type 1 (AT1) receptor blocker, but not affected by PD123319, an Ang II type 2 (AT2) receptor antagonist. These findings present evidence that Ang-II-mediated changes in the productions of MMP-1 and TIMP-1 occur via AT1 receptors and a TGF-β-dependent mechanism.