Background: p300, a transcription co-activator, plays an important role in multicellular organisms and inflammation. However, the mechanism of p300 in type 2 diabetes nephropathy (T2DN) remains largely unknown. Our aim is to explore the mechanism of p300 in T2DN.
Methods: A T2DN mice model was induced by db/db transgenic mice or a high fat diet for 24 weeks. The levels of IL-6 and TNF-α were examined by real-time PCR (RT-PCR) in the renal cortex and by an enzyme linked immunosorbent assay (ELISA) in the serum of the T2DN mice. p300 siRNA was used to knockdown the expression of p300, and His-tagged-p300 plasmid was used to overexpress the p300 protein level in podocytes. Hematoxylin-eosin staining (H&E) and Masson trichrome analysis were used to detect the kidney pathology in T2DN.
Results: The levels of IL-6 and TNF-α were significantly increased in T2DN. p300 was significantly increased in T2DN. Consistently, p300 silencing significantly suppressed the inflammatory response and the overexpression of p300 significantly promoted the production of IL-6 and TNF-α in T2DN.
Conclusions: This study demonstrated that the production of IL-6 and TNF-α, and the expression of p300, were increased in T2DN. Furthermore, P300 significantly promoted the activation of the NF-κB subunit p65 through a direct association with p65 in T2DN, subsequently enhancing the production of IL-6 and TNF-α.
Keywords: Inflammation; transcription coactivator p300; type 2 diabetes nephropathy.
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