title: Histone acetyltransferase PCAF regulates inflammatory molecules in the development of renal injury.
abstract: Kidney diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), are associated with inflammation. The mechanism that regulates inflammation in these renal injuries remains unclear. Here, we demonstrated that p300/CBP-associated factor (PCAF), a histone acetyltransferase, was overexpressed in the kidneys of db/db mice and lipopolysaccharide (LPS)-injected mice. Moreover, elevated histone acetylation, such as H3K18ac, and up-regulation of some inflammatory genes, such as ICAM-1, VCAM-1, and MCP-1, were found upon these renal injuries. Furthermore, increased H3K18ac was recruited to the promoters of ICAM-1, VCAM-1, and MCP-1 in the kidneys of LPS-injected mice. In vitro studies demonstrated that PCAF knockdown in human renal proximal tubule epithelial cells (HK-2) led to downregulation of inflammatory molecules, including VCAM-1, ICAM-1, p50 subunit of NF-κB (p50), and MCP-1 mRNA and protein levels, together with significantly decreased H3K18ac level. Consistent with these, overexpression of PCAF enhanced the expression of inflammatory molecules. Furthermore, PCAF deficiency reduced palmitate-induced recruitment of H3K18ac on the promoters of ICAM-1 and MCP-1, as well as inhibited palmitate-induced upregulation of these inflammatory molecules. In summary, the present work demonstrates that PCAF plays an essential role in the regulation of inflammatory molecules through H3K18ac, which provides a potential therapeutic target for inflammation-related renal diseases.
authors.affiliation: a College of Life Sciences ; Wuhan University ; Wuhan , Hubei , China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Danyang
authors.initials: D
authors.lastname: Wan
authors.forename: Jianshuang
authors.initials: J
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D018932:Chemokine CCL2; D006657:Histones; D018799:Intercellular Adhesion Molecule-1; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C491768:Ccl2 protein, mouse; C090509:Icam1 protein, mouse
keywords: AKI, acute kidney injury; CKD, chronic kidney disease; COL4, type IV collagen; GNAT, GCN5-related N-acetyltransferases; HATs, histone acetyltransferases; HDACs, histone deacetylases; HL, hyperlipidemia; ICAM-1, intercellular adhesion molecule-1; LPS, lipopolysaccharide; MCP-1, monocyte chemotactic protein 1; MnSOD, manganese superoxide dismutase; NF-κB, nuclear factor-κB; PCAF; PCAF, p300/CBP-associated factor; TGFβ-1, transforming growth factor β-1; VCAM-1, vascular cell adhesion molecule-1; acute kidney injury; diabetic nephropathy; histone acetylations; inflammation