title: Fructose downregulates miR-330 to induce renal inflammatory response and insulin signaling impairment: Attenuation by morin.
abstract: Fructose induces insulin resistance with kidney inflammation and injury. MicroRNAs are emerged as key regulators of insulin signaling. Morin has insulin-mimetic effect with the improvement of insulin resistance and kidney injury. This study investigated the protective mechanisms of morin against fructose-induced kidney injury, with particular focus on miR-330 expression change, inflammatory response, and insulin signaling impairment.
  
  
  
  miR-330, sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR)1/3 signaling, nuclear factor-κB (NF-κB)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, and insulin signaling were detected in kidney cortex of fructose-fed rats and fructose-exposed HK-2 cells, respectively. Whether miR-330 mediated inflammatory response to affect insulin signaling was examined using SphK1 inhibitor, S1PR1/3 short interfering RNA, or miR-330 mimic/inhibitor, respectively. Fructose was found to downregulate miR-330 expression to increase SphK1/S1P/S1PR1/3 signaling, and then activate NF-κB/NLRP3 inflammasome to produce IL-1β, causing insulin signaling impairment. Moreover, morin upregulated miR-330 and partly attenuated inflammatory response and insulin signaling impairment to alleviate kidney injury.
  
  
  
  These findings suggest that morin protects against fructose-induced kidney insulin signaling impairment by upregulating miR-330 to reduce inflammatory response. Morin may be a potential therapeutic agent for the treatment of kidney injury associated with fructose-induced inflammation and insulin signaling impairment.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Song
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Yan-Zi
authors.initials: YZ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, P. R. China.
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D005632:Fructose / Q000009:adverse effects*; D005786:Gene Expression Regulation; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008297:Male; D035683:MicroRNAs; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009393:Nephritis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000099157:Sphingosine Kinase; D047309:Flavones
chemical_list: D005419:Flavonoids; D005632:Fructose; D058847:Inflammasomes; D007328:Insulin; D035683:MicroRNAs; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase; C000627115:MIRN330 microRNA, rat; C453881:NLRP3 protein, human; C008548:morin; D047309:Flavones
keywords: Fructose; Kidney injury; Morin; SphK1; miRNA-330