Protective effects of SOCS3 overexpression in high glucose-induced lung epithelial cell injury through the JAK2/STAT3 pathway

Previous studies have suggested that the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway is involved in hyperglycemia-induced lung injury. The present study aimed to investigate the roles of suppressor of cytokine signaling3 (SOCS3) in the regulation of JAK2/STAT3 activation following high glucose (HG) treatment in A549 human pulmonary epithelial cells. Cell viability was evaluated using Cell Counting Kit-8 and lactate dehydrogenase assays. HG-induced inflammatory injury in A549 cells was assessed through the evaluation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels using ELISA. The protein expression levels of SOCS3, JAK2, STAT3, phosphorylated (p)-JAK2 and p-STAT3 were determined using western blot analysis. Cellular viability was significantly decreased, whereas IL-6 and TNF-α levels were significantly increased, following HG stimulation of A549 cells. In addition, the protein levels of SOCS3, p-JAK2 and p-STAT3 were significantly increased in HG-treated cells. Treatment with the JAK2/STAT3 inhibitor tyrphostin AG490, or SOCS3 overexpression, appeared to prevent the HG-induced alterations in protein expression. Furthermore, cellular viability was enhanced, whereas the levels of proinflammatory cytokines were suppressed. These finding suggested the involvement of the SOCS3/JAK2/STAT3 signaling pathway in HG-induced responses in lung cells. Therefore, it may be hypothesized that the inhibition of the JAK2/STAT3 pathway through SOCS3 overexpression may prevent hyperglycemia-induced lung injury, and may have therapeutic potential for the treatment of patients with diabetic lung injury.