title: Effect of angiotensin type 2 receptor over-expression on the rat mesangial cell fibrotic phenotype: effect of gender.
abstract: OBJECTIVE
  The protective role of angiotensin type 2 receptors (AT2-Rs) is still controversial. As AT2-Rs are minimally expressed in adult tissues the aim of the current study was to over-express AT2-Rs in rat mesangial cells in order to ascertain their potential role in modulating renal scarring.
  
  
  METHODS
  Male and female mesangial cells were transiently transfected with AT2-R or control vector then 'injured' with macrophage-conditioned medium (MCM). Culture supernatants and extracted RNA were analysed for evidence of an anti-fibrotic phenotype.
  
  
  RESULTS
  Supernatant fibronectin levels in female mesangial cells treated with MCM were reduced in AT2-R transfected cells (p < 0.001) compared to controls. AT2-R transfected male cells showed a trend towards lower constitutive fibronectin levels. There was no effect of AT2-R transfection on TGF-β or TNF-α secretion; however, IL-1β levels were reduced in male cells treated with MCM. RT-PCR demonstrated that constitutive kallikrein mRNA levels were suppressed in both male and female AT2-R transfected cells. Bradykinin receptors (BkB2-R and BkB1-R) were unaffected in female cells although the BkB1-R was upregulated in male cells treated with MCM.
  
  
  CONCLUSIONS
  This data provides a case for AT2 receptors playing a protective role in rat mesangial cells independent of the effects of blood pressure control.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK. izap1@le.ac.uk
authors.forename: Izabella Z A
authors.initials: IZ
authors.lastname: Pawluczyk
authors.forename: Kevin P G
authors.initials: KP
authors.lastname: Harris
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D050527:Mesangial Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D014162:Transfection
chemical_list: D016207:Cytokines; D005353:Fibronectins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D018002:Receptors, Bradykinin; D019001:Nitric Oxide Synthase; D007610:Kallikreins; D020782:Matrix Metalloproteinases