title: Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy.
abstract: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yan
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China; Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Li
authors.identifier: 0000-0002-4081-635X
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Bioinformatics, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
authors.affiliation: Chongqing Red Cross Hospital, Chongqing 400016, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Handeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Peng
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Tianhui
authors.initials: T
authors.lastname: Wu
authors.affiliation: The Second Clinical College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: The Second Clinical College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Duan
authors.affiliation: The Second Clinical College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The Second Clinical College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: The First Clinical College, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Lijiang
authors.initials: L
authors.lastname: Wei
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China; Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zheng
authors.identifier: 0000-0002-0062-517X
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D044950:Flavanones; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; C005273:naringenin