Renal tubular epithelial cells express osteonectin in vivo and in vitro.
Osteonectin (SPARC, culture shock protein, BM-40) is a widely distributed glycoprotein which binds calcium and several extracellular matrix proteins, including interstitial collagens and thrombospondin, but whose physiologic role remains undefined. In the present studies, we have demonstrated that immunoreactive osteonectin is present in the distal cortical tubule and medullary tubules of murine kidney. We surveyed the renal epithelial cell lines LLC-PK1, MDCK, and OK for the expression of mRNA encoding osteonectin. We found that osteonectin mRNA is expressed by LLC-PK1 and OK cells but not by MDCK cells, as well as by adult kidney from several species. Calcitonin and vasopressin, agents which increase cAMP in these cells, were found to decrease steady-state osteonectin mRNA concentrations. We found that LLC-PK1 cells produced osteonectin protein, that the protein was localized to intracellular granules, and that the protein bound hydroxyapatite in vitro. Pulse-chase analysis revealed that osteonectin was secreted from the cell layer to the medium after a lag time of four to six hours and was secreted preferentially from the basolateral domain of the cell. The preferential secretion of the calcium-binding protein osteonectin from the renal epithelial cell is consistent with several possible functions, including a structural extracellular matrix protein, a participant in transepithelial ion transport, and an inhibitor of extracellular calcification.
Kopp
J B
JB
Bone Research Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland.
Bianco
P
P
Young
M F
MF
Termine
J D
JD
Robey
P G
PG
D000818:Animals; D002460:Cell Line; D017886:Durapatite; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D006728:Hormones / Q000494:pharmacology; D006882:Hydroxyapatites / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D006728:Hormones; D006882:Hydroxyapatites; D015676:Osteonectin; D012333:RNA, Messenger; D017886:Durapatite