title: Differential expression and therapeutic efficacy of microRNA-346 in diabetic nephropathy mice.
abstract: Diabetic nephropathy (DN) is a major cause of end-stage renal disease, in which the SMAD signaling pathway plays an important role. The aim of the present study was to identify differentially expressed microRNAs (miRNAs) during the progression of DN and to investigate a selected miRNA in relation to SMAD3/4 and its therapeutic efficacy. The miRNA microarray was used to identify differentially expressed miRNAs indb/dbDN mice. Reverse transcription-quantitative polymerase chain reaction and immunoblot analyses were used to detect SMAD3/4 expression. The development of DN in thedb/dbmice was demonstrated by glucose dysregulation and typical morphological changes in the kidney. miRNA-346 (miR-346) was identified as one of the differentially expressed miRNAs. The expression of SMAD3/4 was significantly attenuated by miR-346 administration and the therapeutic effects of miR-346 were observed in the DN mouse models. miR-346 was identified as a negative regulator of SMAD3/4. SMAD3/4 was upregulated in the renal tissue ofdb/dbmice. The administration of miR-346 attenuated the SMAD3/4 expression in renal tissue and ameliorated the renal function and glomerular histology in DN mice. This study paves the way for clinical studies of miR-346 in DN.
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Department of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Hou-Qin
authors.initials: HQ
authors.lastname: Xiao
authors.affiliation: The Research Center for High Altitude Medicine, Medical College, Qinghai University, Xining, Qinghai 810001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Hubei Key Laboratory of Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Zhuo-Shun
authors.initials: ZS
authors.lastname: Yang
authors.affiliation: Hubei Key Laboratory of Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China ; Department of Surgery, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
authors.forename: Long-Jun
authors.initials: LJ
authors.lastname: Dai
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Xu
keywords: diabetes; diabetic nephropathy; microRNA microarray; microRNA-346