Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26061546
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Heterogeneity of epigenetic changes at ischemia/reperfusion- and
endotoxin-induced acute kidney injury genes
#MMPMID26061546
Mar D
; Gharib SA
; Zager RA
; Johnson A
; Denisenko O
; Bomsztyk K
Kidney Int
2015[Oct]; 88
(4
): 734-44
PMID26061546
show ga
Aberrant gene expression is a molecular hallmark of acute kidney injury (AKI). As
epigenetic processes control gene expression in a cell- and environment-defined
manner, understanding the epigenetic pathways that regulate genes altered by AKI
may open vital new insights into the complexities of disease pathogenesis and
identify possible therapeutic targets. Here we used matrix chromatin
immunoprecipitation and integrative analysis to study 20 key permissive and
repressive epigenetic histone marks at transcriptionally induced Tnf, Ngal,
Kim-1, and Icam-1 genes in mouse models of AKI; unilateral renal
ischemia/reperfusion, lipopolysaccharide (LPS), and their synergistically
injurious combination. Results revealed unexpected heterogeneity of
transcriptional and epigenetic responses. Tnf and Ngal were transcriptionally
upregulated in response to both treatments individually, and to combination
treatment. Kim-1 was induced by ischemia/reperfusion and Icam-1 by LPS only.
Epigenetic alterations at these genes exhibited distinct time-dependent changes
that shared some similarities, such as reduction in repressive histone
modifications, and also had major ischemia/reperfusion versus endotoxin
differences. Thus, diversity of changes at AKI genes in response to different
insults indicates involvement of several epigenetic pathways. This could be
exploited pharmacologically through rational-drug design to alter the course and
improve clinical outcomes of this syndrome.
free
free
free
