Nitro-oleic acid inhibits the high glucose-induced epithelial-mesenchymal transition in peritoneal mesothelial cells and attenuates peritoneal fibrosis.

As an electrophilic nitroalkene fatty acid, nitro-oleic acid (OA-NO) exerts multiple biological effects that contribute to anti-inflammation, anti-oxidative stress, and antiapoptosis. However, little is known about the role of OA-NO in peritoneal fibrosis. Thus, in the present study, we examined the effects of OA-NO on the high glucose (HG)-induced epithelial-mesenchymal transition (EMT) in human peritoneal mesothelial cells (HPMCs) and evaluated the morphological and immunohistochemical changes in a rat model of peritoneal dialysis-related peritoneal fibrosis. In in vitro experiments, we found that HG reduced the expression level of E-cadherin and increased Snail, N-cadherin, and α-smooth muscle actin expression levels in HPMCs. The above-mentioned changes were attenuated by pretreatment with OA-NO. Additionally, OA-NO also inhibited HG-induced activation of the transforming growth factor-β/Smad signaling pathway and NF-κB signaling pathway. Meanwhile, OA-NO inhibited HG-induced phosphorylation of Erk and JNK. The results from the in vivo experiments showed that OA-NO notably relieved peritoneal fibrosis by decreasing the thickness of the peritoneum; it also inhibited expression of transforming growth factor-β, α-smooth muscle actin, N-cadherin, and vimentin and enhanced expression of E-cadherin in the peritoneum. Collectively, these results suggest that OA-NO inhibits the HG-induced epithelial-mesenchymal transition in HPMCs and attenuates peritoneal dialysis-related peritoneal fibrosis.