Transcription coactivator p300 promotes inflammation by enhancing p65 subunit activation in type 2 diabetes nephropathy.

ABSTRACT: 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-? 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-? 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-? in T2DN. CONCLUSIONS:This study demonstrated that the production of IL-6 and TNF-?, and the expression of p300, were increased in T2DN. Furthermore, P300 significantly promoted the activation of the NF-?B subunit p65 through a direct association with p65 in T2DN, subsequently enhancing the production of IL-6 and TNF-?.

SUBMITTER: Lan F 

PROVIDER: S-EPMC6947128 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature