Effect of angiotensin type 2 receptor over-expression on the rat mesangial cell fibrotic phenotype: effect of gender

Background and aim: 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. Conclusion: This data provides a case for AT2 receptors playing a protective role in rat mesangial cells independent of the effects of blood pressure control.