Contribution of High Mobility Group Box 1 to Nicotine-Induced Podocyte Injury and Glomerular Sclerosis

Abstract ID 95360 Poster Board 065 Cigarette smoking, a well-established risk factor for many diseases, plays a pivotal role in the incidence and progression of renal dysfunction. Smoking associated renal damage bears distinct physiological correlations in conditions such as diabetic nephropathy and obesity-induced glomerulopathy. However, the cellular and molecular basis of such an association remains poorly understood. High mobility group box 1 (HMGB1) is a highly conserved non-histone chromatin associated protein that largely contributes to the pathogenesis of chronic inflammatory and autoimmune diseases such as sepsis, atherosclerosis, and chronic kidney diseases. Hence, the present study tested whether high mobility group box 1 (HMGB1) contributes to nicotine-induced podocyte injury and glomerular sclerosis. In in vitro, biochemical analysis showed that nicotine treatment significantly increased the HMGB1 release compared to vehicle treated podocytes. However, prior treatment with glycyrrhizin, an HMGB1 binder abolished the nicotine-induced HMGB1 release in podocytes. Furthermore, western blot or immunofluorescent analysis showed that nicotine treatment significantly decreased the expression of nephrin and podocin compared to control cells. However, prior treatment with glycyrrhizin attenuated the nicotine-induced nephrin and podocin reduction. In addition, nicotine treatment significantly increased the toll like receptor 4 (TLR4), desmin expression and cell permeability compared to vehicle treated podocytes. However, prior treatment with glycyrrhizin attenuated the nicotine induced TLR4, desmin expression and cell permeability. In in vivo studies, Western blot and biochemical analysis showed that nicotine treatment significantly increased the HMGB1, TLR4, urinary protein, urinary albumin, glomerular damage index in nicotine treated mice compared to control mice. However, such nicotine-induced increase of HMGB1, TLR4, urinary protein, urinary albumin and glomerular damage index was significantly attenuated in glycyrrhizin treated mice. Based on these results, it is concluded that HMGB1 is one of the important mediators of nicotine-induced podocyte injury and glomerular sclerosis.