SOCS3 overexpression inhibits advanced glycation end product-induced EMT in proximal tubule epithelial cells

Diabetic nephropathy (DN) is among the most severe complications of diabetes mellitus, and may lead to end‑stage renal disease. Sustained exposure to advanced glycation end products (AGEs) typically causes renal tubular epithelial cells (TECs) to suffer from an epithelial-to-mesenchymal transition (EMT). However, there remains no consensus regarding the mechanism underlying the cause of EMT in TECs as induced by AGEs. In the present study, we investigated the promotion of EMT in TECs by AGEs, and the activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. In addition, we constructed a recombinant adenovirus (Ad) that overexpressed suppressor of cytokine signaling 3 (SOCS3), and examined the regulatory role of SOCS3 in the activation of JAK/STAT signaling and the promotion of EMT in TECs. The results demonstrated that AGE‑bovine serum albumin (BSA) treatment significantly promoted the expression of EMT‑associated proteins, while reducing the expression of the epithelial cell marker, E‑cadherin. Furthermore, the Ad‑mediated SOCS3 overexpression markedly inhibited the AGE‑BSA‑induced JAK2/STAT3 activation; phosphorylated JAK2 and phosphorylated STAT3 expression levels were reduced by the Ad‑SOCS3 infection, compared with the control Ad (Ad‑con) infection, in HK‑2 cells subject to AGE‑BSA. Moreover, the overexpression of SOCS3 markedly inhibited the AGE‑BSA‑promoted EMT in HK‑2 cells. AGE‑BSA‑promoted EMT‑associated proteins, such as α‑smooth muscle actin and collagen I, were reduced by the Ad‑SOCS3 virus infection, in contrast to the Ad‑con virus infection. Furthermore, reduced E-cadherin expression was reversed by the Ad‑SOCS3 virus infection, in contrast to the Ad‑con virus infection, in epithelial HK-2 cells. In conclusion, the present study confirmed the inhibitory role of SOCS3 in the AGE‑induced EMT in renal TECs, implying the protective role of SOCS3 in DN.