Mesangial Cells in Lupus Nephritis

Mesangial cells are critical for the proper function of the glomerulus, playing roles in structural support and injury repair. However, they are also early responders to glomerular immune complex deposition and contribute to inflammation and fibrosis in lupus nephritis. This review highlights recent studies identifying signaling pathways and mediators in mesangial cell response to lupus-relevant stimuli.

Anti-dsDNA antibodies, serum, or plasma from individuals with lupus nephritis, or specific pathologic factors activated multiple signaling pathways. These pathways largely included JAK/STAT/SOCS, PI3K/AKT, and MAPK and led to induction of proliferation and expression of multiple proinflammatory cytokines, growth factors, and profibrotic factors. NFκB activation was a common mediator of response. Mesangial cells proliferate and express a wide array of proinflammatory/profibrotic factors in response to a variety of lupus-relevant pathologic stimuli. While some of the responses are similar, the mechanisms involved appear to be diverse depending on the stimulus. Future studies are needed to fully elucidate these mechanisms with respect to the diverse milieu of stimuli.