title: FKBP-12 exhibits an inhibitory activity on calcium oxalate crystal growth in vitro.
abstract: Urolithiasis and calcium oxalate crystal deposition diseases are still significant medical problems. In the course of nephrocalcin cDNA cloning, we have identified FKBP-12 as an inhibitory molecule of calcium oxalate crystal growth. lambdagt 11 cDNA libraries were constructed from renal carcinoma tissues and screened for nephrocalcin cDNA clones using anti-nephrocalcin antibody as a probe. Clones expressing recombinant proteins, which appeared to be antigenically cross-reactive to nephrocalcin, were isolated and their DNA sequences and inhibitory activities on the calcium oxalate crystal growth were determined. One of the clone lambda gt 11 #31-1 had a partial fragment (80 bp) of FKBP-12 cDNA as an insert. Therefore, a full-length FKBP-12 cDNA was PCR-cloned from the lambda gt 11 renal carcinoma cDNA library and was subcloned into an expression vector. The resultant recombinant FKBP-12 exhibited an inhibitory activity on the calcium oxalate crystal growth (Kd=10(-7) M). Physiological effect of the extracellular FKBP-12 was investigated in terms of macrophage activation and proinflammatory cytokine gene induction. Extracellular FKBP-12 failed to activate macrophages even at high concentrations. FKBP-12 seems an anti-stone molecule for the oxalate crystal deposition disease and recurrent stone diseases.
authors.affiliation: Department of Immunology, Institute for Medical Science, Keimyung University, Taegu, Korea.
authors.forename: In Sook
authors.initials: IS
authors.lastname: Han
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Suh
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Suh
authors.forename: Song Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Su Yul
authors.initials: SY
authors.lastname: Ahn
authors.forename: Byung Kil
authors.initials: BK
authors.lastname: Choe
mesh_terms: D000818:Animals; D001483:Base Sequence; D002129:Calcium Oxalate / Q000037:antagonists & inhibitors*; D002292:Carcinoma, Renal Cell; D003460:Crystallization; D018076:DNA, Complementary; D005110:Extracellular Space; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007669:Kidney Calculi / Q000517:prevention & control*; D007680:Kidney Neoplasms; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D022061:Tacrolimus Binding Protein 1A / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; C029490:nephrocalcin; D002129:Calcium Oxalate; D022061:Tacrolimus Binding Protein 1A