Jixuepaidu Tang-1 inhibits epithelial-mesenchymal transition and alleviates renal damage in DN mice through suppressing long non-coding RNA LOC498759.

Jixuepaidu Tang-1 is obtained from the decoction of the Chinese traditional medicinal plants including Centella asiatica, Astragalus membranaceus, and Sanguis draconis. Transforming growth factor-β1 (TGF-β1)/serum- and glucocorticoid-inducible kinase-1 (SGK1)-induced epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). In addition, long non-coding RNAs (lnRNAs) participate in the development of DN, but the role of lncRNA LOC498759 in DN is still unclear. This study aims to investigate the role of Jixuepaidu Tang-1 in regulating podocyte injury and renal damage in DN and to validate whether the mechanisms involve TGF-β1/SGK1 signaling and LOC498759. The drug treatment was initiated 2 weeks after the DN modeling. The MTT method and TUNEL staining were used to measure cell viability and apoptosis, respectively. Immunofluorescence staining was used to detect the expression of nephrin and desmin in podocytes. Sera from the Jixuepaidu Tang-1-treated mice reversed the high glucose (HG)-induced podocyte injury and EMT in mouse podocytes. Further in vivo assay revealed that Jixuepaidu Tang-1 not only reduced the ratio of the kidney to body weight, 24 h-urine total protein, and blood glucose, but alleviated glomerular mesangial extracellular matrix deposition and glomerular cell apoptosis in the streptozotocin-induced DN mice. Mechanically, the mechanisms of Jixuepaidu Tang-1 may involve the suppression of EMT by inhibiting the TGF-β1/SGK1-induced LOC498759 expression. Collectively, Jixuepaidu Tang-1 attenuates podocyte injury and renal damage in DN, and inhibits EMT through suppressing TGF-β1/SGK1-LOC498759 signaling.