Silencing PEG3 inhibits renal fibrosis in a rat model of diabetic nephropathy by suppressing the NF-κB pathway.

As paternally expressed gene 3 (PEG3), which can activate NF-κB pathway, plays an important role in the development of renal fibrosis in diabetic nephropathy (DN), the present study aimed to investigate the interaction of PEG3 and the NF-κB pathway on renal fibrosis in a DN model. Following the induction of the rat model of DN, a series of experiments were used to measure serum creatinine (Scr), blood urea nitrogen (BUN), urine protein for 24 h (UP24 h), proliferation of renal fibroblasts, positive expression of PEG3, Collagen I and Collagen II protein, the activity of NF-κB, collagen fiber expression and the FSP1 cell ratio (fibroblast marker, reflecting renal fibrosis). Silencing of PEG3 or inhibition of the NF-κB pathway decreased the levels of Scr, BUN, and UP24 h, down-regulated Collagen I protein and up-regulated Collagen II protein. These treatments also down-regulated the expression of PEG3, NF-κB, Vimentin, α-SMA, FN, caspase-3 and FSP1 and the extents of IκBα, inhibitor of kappa B (IκB) kinase β (IKKβ), and NF-κB p65 phosphorylation while that of E-cadherin was up-regulated, and the ratio of FSP1 cells was decreased. Taken together, these results showed that silencing of PEG3 inhibited the NF-κB pathway, thereby alleviating renal fibrosis in DN, thus presenting PEG3 as a potential therapeutic target in renal fibrosis in DN.