Renal inter-alpha-trypsin inhibitor heavy chain 3 increases in calcium oxalate stone-forming patients.
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.
Evan
A P
AP
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46223, USA. evan@anatomy.iupui.edu
Bledsoe
S
S
Worcester
E M
EM
Coe
F L
FL
Lingeman
J E
JE
Bergsland
K J
KJ
D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000378:metabolism*; D002129:Calcium Oxalate / Q000737:chemistry / Q000652:urine*; D003460:Crystallization; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007685:Kidney Tubules, Collecting / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008138:Loop of Henle / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism; D014545:Urinary Calculi / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
D000510:Alpha-Globulins; C016001:alpha-1-microglobulin; D053495:Osteopontin; D002129:Calcium Oxalate; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid