title: MicroRNA profiles in allograft tissues and paired urines associate with chronic allograft dysfunction with IF/TA.
abstract: Despite the advances in immunosuppression, renal allograft attrition over time remains unabated due to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA). We aimed to evaluate microRNA (miRNA) signatures in CAD with IF/TA and appraise correlation with paired urine samples and potential utility in prospective evaluation of graft function. MiRNA signatures were established between CAD with IF/TA versus normal allografts by microarray. Validation of the microarray results and prospective evaluation of urine samples was performed using real-time quantitative-PCR (RT-qPCR). Fifty-six miRNAs were identified in samples with CAD-IF/TA. Five miRNAs were selected for further validation based on array fold change, p-value and in silico predicted mRNA targets. We confirmed the differential expression of these five miRNAs by RT-qPCR using an independent set of samples. Differential expression was detected for miR-142-3p, miR-204, miR-107 and miR-211 (p < 0.001) and miR-32 (p < 0.05). Furthermore, differential expression of miR-142-3p (p < 0.01), miR-204 (p < 0.01) and miR-211 (p < 0.05) was also observed between patient groups in urine samples. A characteristic miRNA signature for IF/TA that correlates with paired urine samples was identified. These results support the potential use of miRNAs as noninvasive markers of IF/TA and for monitoring graft function.
authors.affiliation: Surgery Biostatistics Human and Molecular Genetics Pathology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Scian
authors.forename: D G
authors.initials: DG
authors.lastname: Maluf
authors.forename: K G
authors.initials: KG
authors.lastname: David
authors.forename: K J
authors.initials: KJ
authors.lastname: Archer
authors.forename: J L
authors.initials: JL
authors.lastname: Suh
authors.forename: A R
authors.initials: AR
authors.lastname: Wolen
authors.forename: M U
authors.initials: MU
authors.lastname: Mba
authors.forename: H D
authors.initials: HD
authors.lastname: Massey
authors.forename: A L
authors.initials: AL
authors.lastname: King
authors.forename: T
authors.initials: T
authors.lastname: Gehr
authors.forename: A
authors.initials: A
authors.lastname: Cotterell
authors.forename: M
authors.initials: M
authors.lastname: Posner
authors.forename: V
authors.initials: V
authors.lastname: Mas
mesh_terms: D000328:Adult; D001483:Base Sequence; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D014184:Transplantation, Homologous; D014556:Urine
chemical_list: D035683:MicroRNAs; D003404:Creatinine