Suppression of Gremlin by RNA interference attenuates glucose-induced fibrogenesis in rat mesangial cells

Background: diabetic nephropathy (DN) is the most common cause of end-stage of renal disease. It is beneficial for us to find effective way to treat the disease. Gremlin is deemed as a key factor in the development of diabetic nephropathy at present. We hypothesized that the pathological changes might be prevented by eliminating Gremlin function in high glucose-induced renal fibrosis. Methods: lentiviral vector targeting Gremlin was applied to inhibit Gremlin expression at a high glucose concentration which simulated diabetic nephropathy in rat mesangial cells. Results: the shRNA vector, designated shGremlin, significantly inhibited Gremlin expression in rat mesangial cells cultured under high glucose conditions. Increase in BMP-7 as well as its downstream genes or proteins including phospholated Smad 1/5/8, type IV collagen and fibronectin was observed. Conclusions: our work provides a valuable method to prevent glomerular/renal fibrosis with RNA interference, and also enable development of new therapies that target Gremlin.