SPARC regulates processing of procollagen I and collagen fibrillogenesis in dermal fibroblasts
SPARC regulates processing of procollagen I and collagen fibrillogenesis in dermal fibroblasts
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DOI：
10.1074/jbc.m700167200
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发表时间：
2007-07-27
影响因子：
4.8
通讯作者：
Bradshaw, Amy D.
中科院分区：
文献类型：
--
作者：
Rentz, Tyler J.;Poobalarahi, Felicitta;Bradshaw, Amy D.
控制胶原纤维形成的因素的表征对于理解组织组织结构和导致纤维化的机制至关重要。分泌蛋白（分泌的酸性蛋白质，富含半胱氨酸）是一种结合胶原蛋白的反粘附蛋白。在本文中，我们表明，胶原纤维在SPARC-无效的皮肤从小鼠1个月大的纤维聚集和积累在直径范围为60-70 nm，在胶原纤维生长的建议中间无效。在体外，由SPARC-空真皮成纤维细胞产生的前胶原I表现出与细胞层的初始优先关联，与野生型成纤维细胞产生的相比。然而，由SPARC-空细胞产生的胶原蛋白I不能有效地掺入洗涤剂不溶性组分中。与细胞缔合的初始增加一致，与野生型细胞相比，在SPARC-空细胞中以加工形式存在更大量的总胶原蛋白I。添加重组的NTA逆转了I型胶原与细胞层的结合，并减少了SPARC-null细胞中I型前胶原的加工。尽管胶原纤维在SPARC-null成纤维细胞的表面上比在野生型细胞上更早形成，但SPARC-null成纤维细胞上的纤维并不持久。我们的结论是，cardiac介导的协会的前胶原I与细胞，以及其加工和纳入细胞外基质。
A characterization of the factors that control collagen fibril formation is critical for an understanding of tissue organization and the mechanisms that lead to fibrosis. SPARC (secreted protein acidic and rich in cysteine) is a counter-adhesive protein that binds collagens. Herein we show that collagen fibrils in SPARC-null skin from mice 1 month of age were inefficient in fibril aggregation and accumulated in the diameter range of 60-70 nm, a proposed intermediate in collagen fibril growth. In vitro, procollagen I produced by SPARC-null dermal fibroblasts demonstrated an initial preferential association with cell layers, in comparison to that produced by wild-type fibroblasts. However, the collagen I produced by SPARC-null cells was not efficiently incorporated into detergent-insoluble fractions. Coincident with an initial increase in cell association, greater amounts of total collagen I were present as processed forms in SPARC-null versus wild-type cells. Addition of recombinant SPARC reversed collagen I association with cell layers and decreased the processing of procollagen I in SPARC-null cells. Although collagen fibers formed on the surface of SPARC-null fibroblasts earlier than those on wildtype cells, fibers on SPARC-null fibroblasts did not persist. We conclude that SPARC mediates the association of procollagen I with cells, as well as its processing and incorporation into the extracellular matrix.