Junghyun Kim1, Eunjin Sohn, Chan-Sik Kim, Kyuhyung Jo, Jin Sook Kim. 1. Diabetic Complications Research Center, Division of Traditional Korean Medicine Integrated Research, Korea Institute of Oriental Medicine, Daejeon, South Korea.
Abstract
BACKGROUND/AIMS: The purpose of the experiment reported here was to assess the involvement of high-mobility group box-1 (HMGB1), receptor for advanced glycation end products (RAGE) and nuclear factor (NF)-κB signaling pathway in the development of rat diabetic nephropathy. METHODS: Diabetes was induced by intraperitoneal streptozotocin injection in 7-week-old male rats. At 20 weeks of age, renal expression of HMGB1 was detected by immunohistochemistry. The expression of RAGE and NF-κB activity was studied by Western blot and electrophoretic mobility shift assay in renal tissues of normoglycemic and diabetic rats, respectively. RESULTS: HMGB1 was highly expressed in both the cytoplasmic and nuclear patterns in diabetic renal glomerular cells and tubular epithelial cells, although in normal rats, HMGB1 was expressed only in the cell nuclei. The expression of RAGE, a potential receptor for HMGB1, and NF-κB activity were also greater in diabetic than in normal rats. Moreover, diabetes increased the binding of NF-κB to the RAGE promoter. CONCLUSION: These findings suggest that hyperglycemia-induced HMGB1 release may induce the renal injury in diabetic rats, and that the pathogenic role of HMGB1 might be dependent on RAGE and through activation of NF-κB.
BACKGROUND/AIMS: The purpose of the experiment reported here was to assess the involvement of high-mobility group box-1 (HMGB1), receptor for advanced glycation end products (RAGE) and nuclear factor (NF)-κB signaling pathway in the development of ratdiabetic nephropathy. METHODS:Diabetes was induced by intraperitoneal streptozotocin injection in 7-week-old male rats. At 20 weeks of age, renal expression of HMGB1 was detected by immunohistochemistry. The expression of RAGE and NF-κB activity was studied by Western blot and electrophoretic mobility shift assay in renal tissues of normoglycemic and diabeticrats, respectively. RESULTS:HMGB1 was highly expressed in both the cytoplasmic and nuclear patterns in diabetic renal glomerular cells and tubular epithelial cells, although in normal rats, HMGB1 was expressed only in the cell nuclei. The expression of RAGE, a potential receptor for HMGB1, and NF-κB activity were also greater in diabetic than in normal rats. Moreover, diabetes increased the binding of NF-κB to the RAGE promoter. CONCLUSION: These findings suggest that hyperglycemia-induced HMGB1 release may induce the renal injury in diabeticrats, and that the pathogenic role of HMGB1 might be dependent on RAGE and through activation of NF-κB.
Authors: Deena A Abdulahad; Johanna Westra; Johannes Bijzet; Sebastian Dolff; Marcory C van Dijk; Pieter C Limburg; Cees G M Kallenberg; Marc Bijl Journal: Arthritis Res Ther Date: 2012-08-14 Impact factor: 5.156
Authors: Miroslaw J Szczepanski; Michal Luczak; Ewa Olszewska; Marta Molinska-Glura; Mariola Zagor; Antoni Krzeski; Henryk Skarzynski; Jan Misiak; Karolina Dzaman; Mikolaj Bilusiak; Tomasz Kopec; Malgorzata Leszczynska; Henryk Witmanowski; Theresa L Whiteside Journal: J Mol Med (Berl) Date: 2014-11-12 Impact factor: 4.599