Evan A P, Bledsoe S, Worcester E M, Coe F L, Lingeman J E, Bergsland K J
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46223, USA.
Kidney Int. 2007 Dec;72(12):1503-11. doi: 10.1038/sj.ki.5002569. Epub 2007 Sep 26.
Inter-alpha-trypsin inhibitor heavy-chain proteins bind to the protease inhibitor bikunin and to hyaluronan, stabilizes extracellular matrix in various tissues, and also inhibits calcium oxalate crystallization in vitro. In both normal and stone-forming patients, we found heavy chain 3 and hyaluronan in the interstitial matrix of the kidney. Osteopontin was found in the collecting duct, thin loop of Henle, and urothelial cells. In stone formers, heavy chain 3 was also present in collecting duct, thin loop, and interstitial cells. Heavy chain 3 and osteopontin colocalized in plaque matrix and urothelial cells. Within individual plaque spherules, heavy chain 3 was found in the matrix layer while osteopontin was located along the crystal-matrix interface. Bikunin was present only in the collecting duct apical membranes and the loop cell cytoplasm of stone formers colocalizing with osteopontin and heavy chain 3. Widespread heavy chain 3 was only present in stone formers, whereas osteopontin was similarly expressed in normal and stone-forming subjects except for its localization in plaques of the stone formers. This is consistent with studies linking inter-alpha-trypsin inhibitor components to human stone disease, although their role is still unclear. Heavy chain 3 may also play a role in stabilizing hyaluronan in the renal interstitial matrix.
α-胰蛋白酶抑制剂重链蛋白与蛋白酶抑制剂比基尼和透明质酸结合，稳定各种组织中的细胞外基质，并且在体外还抑制草酸钙结晶。在正常患者和结石形成患者中，我们在肾间质基质中均发现了重链3和透明质酸。在集合管、髓袢细段和尿路上皮细胞中发现了骨桥蛋白。在结石形成者中，重链3也存在于集合管、细段和间质细胞中。重链3和骨桥蛋白在斑块基质和尿路上皮细胞中共定位。在单个斑块小球内，重链3存在于基质层，而骨桥蛋白位于晶体-基质界面处。比基尼仅存在于结石形成者的集合管顶端膜和细段细胞胞质中，与骨桥蛋白和重链3共定位。广泛存在的重链3仅在结石形成者中出现，而骨桥蛋白在正常人和结石形成者中的表达相似，只是在结石形成者的斑块中有其定位。这与将α-胰蛋白酶抑制剂成分与人类结石病联系起来的研究一致，尽管它们的作用仍不清楚。重链3可能在稳定肾间质基质中的透明质酸方面也发挥作用。
