title: Robust shifts in S100a9 expression with aging: a novel mechanism for chronic inflammation.
abstract: The S100a8 and S100a9 genes encode a pro-inflammatory protein (calgranulin) that has been implicated in multiple diseases. However, involvement of S100a8/a9 in the basic mechanisms of intrinsic aging has not been established. In this study, we show that shifts in the abundance of S100a8 and S100a9 mRNA are a robust feature of aging in mammalian tissues, involving a range of cell types including the central nervous system. To identify transcription factors that control S100a9 expression, we performed a large-scale transcriptome analysis of 62 mouse and human cell types. We identified cell type-specific trends, as well as robust associations linking S100a9 coexpression to elevated frequency of ETS family motifs, and in particular, to motifs recognized by the transcription factor SPI/PU.1. Sparse occurrence of SATB1 motifs was also a strong predictor of S100a9 coexpression. These findings offer support for a novel mechanism by which a SPI1/PU.1-S100a9 axis sustains chronic inflammation during aging.
authors: Department of Dermatology, University of Michigan School of Medicine, Ann Arbor, MI 48109-2200, USA. wswindel@umich.edu
authors: William R
authors: WR
authors: Swindell
authors: Andrew
authors: A
authors: Johnston
authors: Xianying
authors: X
authors: Xing
authors: Andrew
authors: A
authors: Little
authors: Patrick
authors: P
authors: Robichaud
authors: John J
authors: JJ
authors: Voorhees
authors: Gary
authors: G
authors: Fisher
authors: Johann E
authors: JE
authors: Gudjonsson
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016922:Cellular Senescence; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1
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