title: Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice.
abstract: OBJECTIVE
  We investigated whether heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K) mediate insulin inhibition of renal Agt expression and prevention of hypertension and kidney injury in an Akita mouse model of type 1 diabetes.
  
  
  METHODS
  Adult male Akita mice (12 weeks old) were treated with insulin implants and killed at week 16. Untreated non-Akita littermates served as controls. The effects of insulin on blood glucose, systolic BP (SBP), renal proximal tubular cell (RPTC) gene expression and interstitial fibrosis were studied. We also examined immortalised rat RPTCs stably transfected with control plasmid or with plasmid containing rat Agt promoter in vitro.
  
  
  RESULTS
  Insulin treatment normalised blood glucose levels and SBP, inhibited renal AGT expression but enhanced hnRNP F, hnRNP K and angiotensin-converting enzyme-2 expression, attenuated renal hypertrophy and glomerular hyperfiltration and decreased urinary albumin/creatinine ratio, as well as AGT and angiotensin II levels, in Akita mice. In vitro, insulin inhibited Agt but stimulated Hnrnpf and Hnrnpk expression in high-glucose media via p44/42 mitogen-activated protein kinase signalling in RPTCs. Transfection with Hnrnpf or Hnrnpk small interfering RNAs prevented insulin inhibition of Agt expression in RPTCs.
  
  
  CONCLUSIONS
  These data indicate that insulin prevents hypertension and attenuates kidney injury, at least in part, through suppressing renal Agt transcription via upregulation of hnRNP F and hnRNP K expression in diabetic Akita mice. HnRNP F and hnRNP K may be potential targets in the treatment of hypertension and kidney injury in diabetes.
authors.affiliation: Centre de recherche, Centre hospitalier de l'Université de Montréal (CHUM)-Hôtel-Dieu Hospital, Université de Montréal, Pavillon Masson, 3850 Saint Urbain Street, Montreal, Canada, QC, H2W 1T8.
authors.forename: S
authors.initials: S
authors.lastname: Abdo
authors.forename: C-S
authors.initials: CS
authors.lastname: Lo
authors.forename: I
authors.initials: I
authors.lastname: Chenier
authors.forename: A
authors.initials: A
authors.lastname: Shamsuyarova
authors.forename: J G
authors.initials: JG
authors.lastname: Filep
authors.forename: J R
authors.initials: JR
authors.lastname: Ingelfinger
authors.forename: S-L
authors.initials: SL
authors.lastname: Zhang
authors.forename: J S D
authors.initials: JS
authors.lastname: Chan
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000517:prevention & control*; D007328:Insulin / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice
chemical_list: D001786:Blood Glucose; D007328:Insulin; D000808:Angiotensinogen