Expression of heat shock protein 90 in the kidneys of diabetic db/db mice

Y.S. Kim, E. Sohn, D.H. Jung, Y.M. Lee, C.S. Kim, J. Kim, J.S. Kim

Korean Medicine-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Republic of Korea. jskim@kiom.re.kr

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• Metabolism

OBJECTIVE: To identify novel genes regulated in diabetic nephropathy.

MATERIALS AND METHODS: Total RNA from the renal cortex of db/+ and db/db mice was isolated and DNA microarrays specific for diabetes signaling pathways were used for expression profiling. Expression of mRNA and protein was determined by RT-PCR and western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling (TUNEL) assay and immunohistochemical staining were assessed in renal cortex of db/db mice.

RESULTS: Microarray data revealed that 7 genes show up- or down-regulated pattern and diabetic mice specifically decreased heat shock protein (Hsp) 90α expression of genes compared to control mice (diabetic mice 0.68 vs. control mice 1 relative density). Expression of Hsp90α mRNA and Hsp90 protein was significantly decreased in the renal cortex of diabetic mice. However, Hsp70 mRNA and protein expression was not changed. Apoptosis was increased in glomeruli of diabetic mice due to increased expression of cleaved caspase-3 and Bax.

CONCLUSIONS: Our results suggest that Hsp 90 expression was decreased in diabetic glomeruli and decreased Hsp90 expression may mediate podocyte apoptosis in type 2 diabetic kidneys.

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