title: Acute kidney injury transcriptomics unveils a relationship between inflammation and ageing.
abstract: There are no pathophysiolgical therapeutic approaches to acute kidney injury (AKI) and the mortality remains high. In addition chronic kidney disease (CKD) predisposes to AKI and AKI contributes to progression of CKD. Recently a transcriptomics approach unveiled a relationship between AKI, inflammation and the regulation of ageing. A transcriptomics analysis of experimental AKI revealed increased kidney expression of Fn14 and transmembrane chemokine CXCL16, as well as a decreased expression of the kidney-secreted anti-ageing hormone Klotho. Fn14 is the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily. In AKI kidneys there was a positive correlation between Fn14 and CXCL16 mRNA expression and an inverse correlation between Fn14 and Klotho mRNA. Tubular cells were the site of Fn14, CXCL16 and Klotho expression in vivo. Research on the relationships between these three molecules disclosed that TWEAK activation of Fn14 promoted inflammation through secretion of chemokines such as CXL16 in tubular cells in culture and in vivo. Furthermore, TWEAK activation of Fn14 decreased expression of Klotho mRNA and protein in culture and in vivo. Interestingly, both TWEAK activation of CXCL16 mRNA transcription and suppression of Klotho mRNA transcription were mediated by the NF&kappa;B transcription factor. In conclusion, TWEAK engagement of Fn14 is a central event promoting NF&kappa;B-mediated activation of inflammation pathways and suppression of anti-inflammatory/anti-ageing pathways. This information may influence future therapeutic approaches to AKI and inflammation/aging.
authors.affiliation: IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid and Fundación Renal Iñigo Álvarez de Toledo. Madrid, Spain.
authors.forename: M Concepción
authors.initials: MC
authors.lastname: Izquierdo
authors.forename: Ana B
authors.initials: AB
authors.lastname: Sanz
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Sánchez-Niño
authors.forename: M Vanessa
authors.initials: MV
authors.lastname: Pérez-Gómez
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Jonay
authors.initials: J
authors.lastname: Poveda
authors.forename: Olga
authors.initials: O
authors.lastname: Ruiz-Andrés
authors.forename: Adrián M
authors.initials: AM
authors.lastname: Ramos
authors.forename: Juan A
authors.initials: JA
authors.lastname: Moreno
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000235:genetics*; D000367:Age Factors; D000375:Aging; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications; D016328:NF-kappa B / Q000502:physiology; D051116:Receptors, Scavenger / Q000235:genetics; D059467:Transcriptome
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D016328:NF-kappa B; D051116:Receptors, Scavenger