Strandjord T P, Madtes D K, Weiss D J, Sage E H
Department of Pediatrics, University of Washington, Seattle, WA 98195-6320, USA.
Am J Physiol. 1999 Sep;277(3):L628-35. doi: 10.1152/ajplung.1999.277.3.L628.
Secreted protein acidic and rich in cysteine (SPARC) has been shown to be coexpressed with type I collagen in tissues undergoing remodeling and wound repair. We speculated that SPARC is required for the accumulation of collagen in lung injury and that its absence would attenuate collagen accumulation. Accordingly, we have assessed levels of collagen in SPARC-null mice in an intratracheal bleomycin-injury model of pulmonary fibrosis. Eight- to ten-week-old SPARC-null and wild-type (WT) mice received bleomycin (0.0035 U/g) or saline intratracheally and were subsequently killed after 14 days. Relative levels of SPARC mRNA were increased 2.7-fold (P < 0.001) in bleomycin-treated WT lungs in comparison with saline-treated lungs. Protein from bleomycin-treated WT lung contained significantly more hydroxyproline (191.9 microg/lung) than protein from either bleomycin-treated SPARC-null lungs or saline-treated WT and SPARC-null lungs (147.4 microg/lung, 125.4 microg/lung, and 113. 0 microg/lung, respectively; P < 0.03). These results indicate that SPARC is increased in response to lung injury and that accumulation of collagen, as indicated by hydroxyproline content, is attenuated in the absence of SPARC. The properties of SPARC as a matricellular protein associated with cell proliferation and matrix turnover are consistent with its participation in the development of pulmonary fibrosis.
富含半胱氨酸的酸性分泌蛋白（SPARC）已被证明在经历重塑和伤口修复的组织中与I型胶原蛋白共表达。我们推测SPARC是肺损伤中胶原蛋白积累所必需的，并且其缺失会减弱胶原蛋白的积累。因此，我们在肺纤维化的气管内博来霉素损伤模型中评估了SPARC基因敲除小鼠体内的胶原蛋白水平。8至10周龄的SPARC基因敲除小鼠和野生型（WT）小鼠经气管内给予博来霉素（0.0035 U/g）或生理盐水，随后在14天后处死。与生理盐水处理的肺相比，博来霉素处理的野生型肺中SPARC mRNA的相对水平增加了2.7倍（P < 0.001）。博来霉素处理的野生型肺组织中的蛋白质所含羟脯氨酸（191.9微克/肺）明显多于博来霉素处理的SPARC基因敲除肺组织或生理盐水处理的野生型和SPARC基因敲除肺组织中的蛋白质（分别为147.4微克/肺、125.4微克/肺和113.0微克/肺；P < 0.03）。这些结果表明，SPARC在肺损伤反应中增加，并且如羟脯氨酸含量所示，在没有SPARC的情况下胶原蛋白的积累会减弱。SPARC作为一种与细胞增殖和基质更新相关的基质细胞蛋白的特性与其参与肺纤维化的发展是一致的。
