title: Elevated levels of beta defensin-1 mRNA in diabetic kidneys of GK rats.
abstract: We previously described the isolation of CDK4, representing the 3(')end of an unknown mRNA, using differential display [Biophys. Res. Commun. 232 (1997) 49]. To determine the identity of the CDK4 gene, full-length CDK4 cDNA clones were isolated from a diabetic kidney cDNA library. DNA sequencing revealed that CDK4 represents the rat beta defensin-1 gene (rBD-1). rBD-1 mRNA was detected in rat kidney, heart, lung, and skeletal muscle using RT-PCR. Using Northern blot analysis, elevated levels of the 0.5kb mRNA transcript were detected in the kidneys of 6-, 16-, 26-, and 40-week-old GK rats when compared with age-matched Wistar controls. A novel 2.0kb mRNA transcript was also detected in all kidneys examined from GK rats in none of the age-matched control kidneys. Biglycan and TGF-beta1 mRNAs were significantly up-regulated in kidneys of GK rats at 26 weeks compared to 16 and 6 weeks, showing that the kidneys of GK rats mimic the gene expression pattern described for human and experimental DN. These data suggest that overexpression of beta-defensin-1 mRNA may play a role in diabetic nephropathy.
authors.affiliation: Molecular Genetics Section, School of Life Sciences, Kings College London, 150 Stamford St., London SE1 9NN, UK.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Page
authors.forename: Afshan N
authors.initials: AN
authors.lastname: Malik
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D058578:Biglycan; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D058575:Decorin; D023082:Defensins / Q000096:biosynthesis / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C546884:BGN protein, human; C546886:Bgn protein, rat; D058578:Biglycan; C546878:DCN protein, human; C406407:DEFB1 protein, human; C546880:Dcn protein, rat; D058575:Decorin; C478968:Defb1 protein, rat; D023082:Defensins; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D023083:beta-Defensins; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases