Renal inter-α-trypsin inhibitor heavy chain 3 increases in calcium oxalate stone-forming patients

A. P. Evan, S. Bledsoe, E. M. Worcester, F. L. Coe, J. E. Lingeman, K. J. Bergsland

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Inter-α-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-α-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.

Original languageEnglish (US)
Pages (from-to)1503-1511
Number of pages9
JournalKidney international
Volume72
Issue number12
DOIs
StatePublished - Dec 2007

Keywords

  • Collecting ducts
  • Electron microscopy
  • Histopathology
  • Kidney biopsy
  • Kidney stones

ASJC Scopus subject areas

  • Nephrology

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    Evan, A. P., Bledsoe, S., Worcester, E. M., Coe, F. L., Lingeman, J. E., & Bergsland, K. J. (2007). Renal inter-α-trypsin inhibitor heavy chain 3 increases in calcium oxalate stone-forming patients. Kidney international, 72(12), 1503-1511. https://doi.org/10.1038/sj.ki.5002569