title: Macrophage migration inhibitory factor is a possible candidate for the induction of microalbuminuria in diabetic db/db mice.
abstract: Preventing the onset of microalbuminuria in diabetic nephropathy is a problem that needs urgent rectification. The use of a mouse model for diabetes is vital in this regard. For example, db/db mice exhibit defects in the leptin receptor Ob-Rb sub-type, while the ob/ob strain exhibits defects in the leptin ligand. These mouse strains demonstrate type 2 diabetes, either with or without microalbuminuria, respectively. The purpose of the present study was to use DNA microarray technology to screen for the gene responsible for the onset of diabetic microalbuminuria. Using Affymetrix Mouse Gene ST 1.0 arrays, microarray analysis was performed using total RNA from the kidneys of ob control, ob/ob, db/m, and db/db mice. Microarray and quantitative reverse transcription-polymerase chain reaction (RT-PCR) indicated that transcription of the macrophage migration inhibitory factor (MIF) gene was significantly enhanced in the kidneys of db/db mice. Western blotting showed that levels of MIF protein was enhanced in the kidneys of both diabetic db/db and ob/ob mice. On the other hand, elevation of urinary MIF excretion detected by enzyme-linked immunosorbent assay (ELISA) was only in db/db mice and preceded the onset of microalbuminuria. Immunofluorescence studies revealed that MIF was expressed in mouse kidney glomeruli. While MIF expression was enhanced in the diabetic kidneys of both mouse strains, the elevated secretion from db/db mouse kidneys may be responsible for initiating the onset of microalbuminuria in diabetic nephropathy.
authors: Faculty of Pharma-Sciences, Teikyo University, Tokyo 173–8605, Japan.
authors: Tamaki
authors: T
authors: Watanabe
authors: Naoko H
authors: NH
authors: Tomioka
authors: Masaru
authors: M
authors: Doshi
authors: Shigekazu
authors: S
authors: Watanabe
authors: Masao
authors: M
authors: Tsuchiya
authors: Makoto
authors: M
authors: Hosoyamada
mesh_terms: D000419:Albuminuria / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007328:Insulin / Q000097:blood; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse