Procollagen II amino propeptide processing by ADAMTS-3 - Insights on dermatosparaxis
Procollagen II amino propeptide processing by ADAMTS-3 - Insights on dermatosparaxis
复制标题
DOI：
10.1074/jbc.m103466200
复制
发表时间：
2001-08-24
影响因子：
4.8
通讯作者：
Apte, SS
中科院分区：
文献类型：
--
作者：
Fernandes, RJ;Hirohata, S;Apte, SS
前胶原I和II的氨基和羧基前肽被特定的酶去除，作为原纤维组装的先决条件。I型前胶原N-前肽酶（ADAMTS-2）的突变通过阻止I型前胶原N-前肽的蛋白水解切除而引起牛的皮肤麻痹和人的Ehlers-Danlos综合征（皮肤麻痹型）。我们发现II型前胶原在皮肤麻痹性鼻软骨中正常加工，这表明存在另一种N-前肽酶。我们研究了ADAMTS-3在Swarm大鼠软骨肉瘤RCS-LTC细胞中的作用，该细胞不能处理II型前胶原N-前肽。用牛ADAMTS-2或人ADAMTS-3稳定转染RCS-LTC细胞部分挽救了加工缺陷，表明ADAMTS-3具有II型前胶原N-前肽酶活性。人皮肤和皮肤成纤维细胞显示ADAMTS-2的mRNA水平比ADAMTS-3高30倍，而人软骨中ADAMTS-3 mRNA比ADAMTS-2 mRNA高5倍。我们建议，ADAMTS-2和ADAMTS-3的过程中的II型前胶原，但ADAMTS-3是生理上更相关的，其首选的表达在软骨。研究结果提供了一个解释的备用软骨dermatosparaxis，也许，为相对备用的一些前胶原I-含有组织。
The amino and carboxyl propeptides of procollagens I and Il are removed by specific enzymes as a prerequisite for fibril assembly. Null mutations in procollagen I N-propeptidase (ADAMTS-2) cause dermatosparaxis in cattle and the Ehlers-Danlos syndrome (dermatosparactic type) in humans by preventing proteolytic excision of the N-propeptide of procollagen I. We have found that procollagen II is processed normally in dermatosparactic nasal cartilage, suggesting the existence of another N-propeptidase(s). We investigated such a role for ADAMTS-3 in Swarm rat chondrosarcoma RCS-LTC cells, which fail to process the procollagen II N-propeptide. Stable transfection of RCS-LTC cells with bovine ADAMTS-2 or human ADAMTS-3 partially rescued the, processing defect, suggesting that ADAMTS-3 has procollagen II N-propeptidase activity. Human skin and skin fibroblasts showed 30-fold higher mRNA levels of ADAMTS-2 than ADAMTS-3, whereas ADAMTS-3 mRNA was 5-fold higher than ADAMTS-2 mRNA in human cartilage. We propose that both ADAMTS-2 and ADAMTS-3 process procollagen II, but ADAMTS-3 is physiologically more relevant, given its preferred expression in cartilage. The findings provide an explanation for the sparing of cartilage in dermatosparaxis and, perhaps, for the relative sparing of some procollagen I-containing tissues.