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ATP-citrate lyase is essential for high glucose-induced histone hyperacetylation and fibrogenic gene up-regulation in mesangial cells

American Journal of Physiology-Renal Physiology. 2017; 
Dilip K. Deb, Yinyin Chen, Jian Sun, Youli Wang and Yan Chun Li
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Proteins were separated by SDS-PAGE and Western blotting was carried out as previously described (24), using the following antibodies: ACL (ab40793, Abcam), phospho-ACL (Ser455) (4331S, Cell Signaling), TGF-β1 (ab92486, Abcam), TGF-β3 (ab15537, Abcam), CTGF (ab6992, Abcam), fibronectin (F6140, Sigma-Aldrich), β−actin (A00702, GenScript), α-tubulin (50407, One World Lab), Histone 3 (06-755, Millipore), H3K9/14Ac (9677, Cell Signaling), H3K18Ac (ab1191, Abcam).

摘要

The goal of this study was to address the role of ATP-citrate lyase (ACL), an enzyme that converts citrate to acetyl-CoA, in high glucose (HG)-induced histone acetylation and pro-fibrotic gene expression. Our recent ChIP-Seq studies have demonstrated that HG induces genome-wide histone hyperacetylation in mesangial cells (MCs). Here we showed that exposure of MCs to HG markedly increased histone acetylation at the H3K9/14 and H3K18 marks and induced the expression of potent pro-fibrotic factors TGF-β1, TGF-β3 and CTGF. The induction of these pro-fibrotic factors was further enhanced by histone deacetylase inhibitor but suppressed by histone acetyl-transferase inhibitor, confirming the importance of hist... More

关键词

Hyperglycemia, glomerulosclerosis, histone acetylation, epigenetic regulation, ATP-citrate 18 lyase.