HMGB1 is activated in type 2 diabetes mellitus patients and in mesangial cells in response to high glucose.

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes, leading the cause of end-stage renal disease (ESRD). And investigations into mechanisms underlying renal inflammation may provide new insight into novel therapeutic targets for patients with DN. However, little is known about the promotion of inflammation in DN. In the present study, we examined the promotion by high glucose to High-mobility group box-1 (HMGB1) in patients with type 2 diabetes mellitus or in renal mesangial SV40 MES 13 cells. Results demonstrated that high glucose promoted the pre-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 in patients with T2DM or in SV40 MES 13 cells. And the serum HMGB1 was also upregulated in T2DM patients, correlating with serum IL-6 and TNFα. The in vitro results indicated that HMGB1 mediated the D-glucose-induced pro-inflammatory cytokines in mesangial cells. And the NF-κB signaling pathway involved in the promotion of pro-inflammatory cytokines by D-glucose. In summary, the present study indicated that HMGB1 was significantly promoted by the glucose in vivo or in vitro, in an association with an upregulation of pro-inflammatory cytokines, via activating NF-κB signaling pathway. And the strategy of HMGB1 inhibition reduced the upregulation of pro-inflammatory cytokines in response to high glucose, via inhibiting the NF-κB signaling pathway. It implies the regulatory role of HMGB1 in the inflammatory responses in DN.