2018
DOI: 10.18632/aging.101453
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Abstract: Dysregulation of gene expression is a hallmark of aging. We examined epigenetic mechanisms that mediate aberrant expression of laminin genes in aging rat kidneys. In old animals, no alterations were found in the levels of abundant laminin mRNAs, whereas Lama3, b3, and c2 transcripts were increased compared to young animals. Lamc2 showed the strongest changes at the mRNA and protein levels. Lamc2 upregulation was transcriptional, as indicated by the elevated RNA polymerase II density at the gene. Furthermore, a… Show more

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Cited by 8 publications
(6 citation statements)
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References 47 publications
(67 reference statements)
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“…25 27 Age-related dysregulation of renal extracellular matrix (ECM) in rats has been shown to be associated with the loss of epigenetic gene silencing as well as with decreased matrix metallopeptidase 2 activity. 28 30 However, it is difficult to determine whether alterations to the membrane are actually causal or simply an effect of early damage at the tubulointerstitial interface. Immunochemical investigations have revealed neither immune complexes nor serum antibody are responsible for basement membrane thickening, and serum from rats with advanced CPN are negative for immunoglobulin G (IgG) or IgM antibodies to kidney antigens.…”
Section: Chronic Progressive Nephropathy Pathogenesis From a Historicmentioning
confidence: 99%
“…DNA methylation is a well-described epigenetic modification in which a methyl group is added at the number five carbon of the cytosine pyrimidine ring in CpG dinucleotides [15,16]. This modification plays a role in genome transcription regulation and is crucial in processes such as the development of multicellular organisms, cell differentiation, regulation of gene expression, X-chromosome inactivation, genomic imprinting, and in the suppression of parasitic and other repeat sequences [15][16][17][18][19][20][21][22][23]. In general, reliable and stable transcriptional silencing is caused if CpG islands (CpGIs)-stretches of DNA that contain an increased frequency of CpG dinucleotides (CG content > 50% and observed/expected CpG ratio > 60%)-in promoter regions are hypermethylated [12,15,16,24,25].…”
Section: Introductionmentioning
confidence: 99%
“…Recently, Denisenko et al (209), in rat old kidneys, found an abnormal epigenetic pattern of extracellular matrix laminins that are involved in the development of glomerulosclerosis and tubulointerstitial fibrosis. In vitro, a predominant role for DNA methylation changes was identified by Bechtel et al (210), who correlated the hypermethylation of RASAL1, a gene encoding an inhibitor of the RAS oncoprotein, with the fibrogenesis in the kidney.…”
Section: Complement and Epigenetic Changes In Agingmentioning
confidence: 99%
“…We compared the gene expression profile and the chromatin accessibility profile during senescence, and found their change trends are corresponding and unified in senescence. For examples, the significantly upregulated genes IGFBP6(Coppe et al, 2010), KLF2(Taniguchi et al, 2012), LAMB3(Denisenko, Mar, Trawczynski, & Bomsztyk, 2018), FOXA1(Q. Li et al, 2013), TGFB1(Senturk et al, 2010), their chromatin accessibility is also increased remarkably with senescence.…”
Section: Resultsmentioning
confidence: 99%
“…Thus, either decreasing or augmenting H3K4 methylation can be detrimental to normal lifespan. Another histone modification, H4K20 trimethylation, is elevated in aged mammalian cells and correlates with impairment in the nuclear lamina [112,113], whereas loss of H3K27 methylation was observed at a subset of upregulated renal genes in aged rats [114].…”
Section: Alterations In Nuclear Organization During Agingmentioning
confidence: 99%