title: MiR-21 Regulates TNF-α-Induced CD40 Expression via the SIRT1-NF-κB Pathway in Renal Inner Medullary Collecting Duct Cells.
abstract: OBJECTIVE
  Recent studies have indicated that microRNA-21 (miR-21) is involved in the inflammatory response in relation to renal disease. Sirtuin1 (SIRT1) exerts renoprotective properties by counteracting inflammation. The activation of CD40 triggers inflammation that participates in renal inflammation and injury. The relationship between miR-21, SIRT1 and CD40, however, remains elusive.
  
  
  METHODS
  Immunohistochemistry, small-interfering RNA (siRNA) transfection, quantitative real-time PCR and western blotting were applied to assess the morphological, functional and molecular mechanisms in primary cultured renal inner medullary collecting duct (IMCD) cells.
  
  
  RESULTS
  TNF-α induced miR-21, CD40 and acetylated-NF-κBp65 (Ac-p65) expressions and reduced SIRT1 expression in IMCD cells. miR-21 mimics increased SIRT1 expression and attenuated Ac-p65 and CD40 expressions in TNF-α-induced IMCD cells, and the corresponding changes were observed with a miR-21 inhibitor. SIRT1 overexpression or activation by SRT1720 diminished TNF-α-induced CD40 and Ac-p65 expressions, which was reversed by SIRT1 siRNA or the inhibitors Ex527 and sirtinol and augmented by pretreatment with NF-κB siRNA. Further study found that the inhibitory effect of miR-21 on Ac-p65 and CD40 expressions was impeded by pretreatment with SIRT1 siRNA.
  
  
  CONCLUSIONS
  The present study indicates that miR-21 inhibits TNF-α-induced CD40 expression in IMCD cells via the SIRT1-NF-κB signalling pathway, which provides new insight in understanding the anti-inflammatory effect of miR-21.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Lin
authors.forename: Yuanwen
authors.initials: Y
authors.lastname: Geng
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.forename: Shuaishuai
authors.initials: S
authors.lastname: Lin
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D007679:Kidney Medulla / Q000166:cytology / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000070416:Antagomirs; D019013:CD40 Antigens; D006576:Heterocyclic Compounds, 4 or More Rings; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C525422:SRT1720; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D056564:Sirtuin 1
keywords: Cluster of differentiation 40; Inflammation; Nuclear factor-kappa B; Renal inner medullary collecting duct (IMCD) cells; SIRT1; microRNA