Renal inter-α-trypsin inhibitor heavy chain 3 increases in calcium oxalate stone-forming patients
Renal inter-α-trypsin inhibitor heavy chain 3 increases in calcium oxalate stone-forming patients
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DOI：
10.1038/sj.ki.5002569
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发表时间：
2007-12-01
影响因子：
19.6
通讯作者：
Bergsland, K. J.
中科院分区：
文献类型：
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作者：
Evan, A. P.;Bledsoe, S.;Bergsland, K. J.
α -胰蛋白酶抑制剂重链蛋白与蛋白酶抑制剂比库宁和透明质酸结合，在各种组织中稳定细胞外基质，并在体外抑制草酸钙结晶。在正常和结石形成的患者中，我们在肾间质基质中发现了重链3和透明质酸。骨桥蛋白见于集管、Henle细袢和尿路上皮细胞。在结石形成者中，重链3也存在于集管、细袢和间质细胞中。重链3和骨桥蛋白共定位于斑块基质和尿路上皮细胞。在单个斑块小球体中，重链3位于基质层，骨桥蛋白位于晶体-基质界面。Bikunin仅存在于集管顶端膜和与骨桥蛋白和重链3共定位的成石细胞的环状细胞质中。广泛存在的重链3只存在于结石形成者中，而骨桥蛋白除了局限于结石形成者的斑块外，在正常和结石形成者中表达相似。这与将α -胰蛋白酶间抑制剂成分与人类结石疾病联系起来的研究是一致的，尽管它们的作用尚不清楚。重链3也可能在稳定肾间质基质中的透明质酸中起作用。
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.