Rat mesangial cells exhibit sex-specific profibrotic and proinflammatory phenotypes

Background. Chronic renal disease progresses more rapidly in males compared to females. This study investigated whether there were any inherent differences between male and female mesangial cells that could contribute to this phenomenon and whether these differences could be modulated by sex hormones. Methods. Experiments were carried out on cultured mesangial cells derived from adult male and female Wistar rat kidneys. Fibronectin, TNF alpha and IL-1 beta levels were measured in control and macrophage-conditioned medium (MCM)-injured cells in the presence and absence of 17 beta estradiol or testosterone. Results. Male mesangial cells expressed higher baseline fibronectin levels compared to female cells. Similarly, basal levels of the proinflammatory cytokines TNF alpha and IL-1 beta were higher in male cells. Fibronectin and IL-1 beta levels were enhanced proportionately between the sexes in response to MCM stimulation, whilst the increase in TNF alpha levels was greater in MCM-stimulated female cells. Treatment with 10(-8) M estradiol down-regulated baseline fibronectin levels in female mesangial cells but had no effect on basal levels in male cells. Estradiol had no effect on MCM-stimulated fibronectin levels in female mesangial cells but further increased stimulated levels in male cells. Testosterone had no effect on basal fibronectin levels of either sex but further enhanced MCM-stimulated fibronectin levels in mesangial cells of both sexes. Sex hormone treatment had no effect on cytokine levels in male mesangial cells. However, in female cells estradiol decreased TNF alpha levels and increased IL-1 beta levels, while testosterone increased the levels of both cytokines. Conclusion. These data would suggest that male mesangial cells inherently exhibit greater profibrotic and proinflammatory characteristics than female cells. The inherent gender phenotypes are further modulated by sex hormones. This sexual dimorphism in mesangial cells may play a contributory role in the faster rate of progression to end-stage renal disease in males.