title: SMILE silencing and PMA activation gene networks in HeLa cells: comparison with kidney transplantation gene networks.
abstract: Recent findings indicated that the SMILE gene may be involved in kidney graft operational tolerance in human. This gene was found to be up-regulated in blood from patients with a well functioning kidney transplant in the absence of immunosuppression compared to other transplanted recipients with clinically different status. A microarray study of SMILE knock-down and phorbol 12-myristate 13-acetate (PMA) activation in HeLa cells was herein compared to our earlier analysis based on microarray data of kidney allograft tolerance and rejection in humans and in a rat model of allograft transplantation to determine possible new genes and gene networks involved in kidney transplantation. The nearest neighbors at the intersection of the SMILE knock-down network with the human tolerance/rejection networks are shown to be NPHS1 and ARRB2, the former (Nephrin) being involved in kidney podocyte function, and the decrease of the latter (Arrestin β2) being recently shown to be involved in monocyte activation during acute kidney allograft rejection in rat. Moreover, another one of the neighbors at the intersection of SMILE network and tolerance/rejection networks is XBP-1, that we report previously to be increased, at a transcript level, after ER stress in SMILE silenced cells. Finally, in this study, we also show that topological properties (both local and global) of joint SMILE knock-down network-tolerance/rejection networks and joint PMA activation network-tolerance/rejection networks in rat and human are essentially different, likely due to the inherent nature of the gene SMILE and the mitogen PMA, that do not act the same way on genes and do not interfere the same way on networks. We also show that interestingly SMILE networks contain more feed-forward loop (FFL) motifs and thus SMILE calls for a more fine-tuned genetic regulation.
authors.affiliation: INSERM U643, Institut de Transplantation Et de Recherche en Transplantation (ITERT), Nantes F-44093, France.
authors.forename: M
authors.initials: M
authors.lastname: Racapé
authors.forename: N
authors.initials: N
authors.lastname: Bragazzi
authors.forename: V
authors.initials: V
authors.lastname: Sivozhelezov
authors.forename: R
authors.initials: R
authors.lastname: Danger
authors.forename: E
authors.initials: E
authors.lastname: Pechkova
authors.forename: J P
authors.initials: JP
authors.lastname: Duong Van Huyen
authors.forename: J P
authors.initials: JP
authors.lastname: Soulillou
authors.forename: S
authors.initials: S
authors.lastname: Brouard
authors.forename: C
authors.initials: C
authors.lastname: Nicolini
mesh_terms: D000818:Animals; D019390:Arrestins / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006084:Graft Rejection / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation; D008565:Membrane Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D000071701:Regulatory Factor X Transcription Factors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D023001:Transplantation Tolerance / Q000235:genetics*; D000071717:X-Box Binding Protein 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605254:ARRB2 protein, human; C000605257:Arrb2 protein, rat; D019390:Arrestins; D050976:Basic-Leucine Zipper Transcription Factors; C411104:CREBZF protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605545:Xbp1 protein, rat; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C113267:nephrin; D013755:Tetradecanoylphorbol Acetate