Renal transcriptome-wide analyses in association with kidney black carbon load

Abstract

Rationale and objectiveInhaled black carbon (BC) has been previously shown to reach and accumulate in the kidneys. As kidneys filter toxicants, they may be susceptible to adverse effects caused by BC accumulation. We studied gene expressions and pathways related to BC particle load in kidney biopsy tissue.Study designGene expression was measured in 29 kidney biopsies performed at one or two years post-transplantation using Affymetrix microarray. We performed a transcriptome-wide association analysis using linear regression analyses, adjusting for individual characteristics to investigate alterations in gene expression in association with kidney BC. Finally, we performed overrepresentation analyses (ConsensusPathDB) to identify enriched pathways and gene ontology sets.ResultsThe geometric mean (5th, 95th percentile) of BC particle levels was 5.4 x 103 (1.5 x 103, 4.1 x 104) number of BC particles per mm(3) kidney tissue. The BC particle load associated with gene expression in overrepresenting pathways related to ciliopathies, macrophage-derived proteins involved in anti-inflammatory response, DNA damage response, TP53 regulation, and necrosis. We identified BC associated genes involved in GO terms ciliogenesis and ciliary structure, including genes involved in the ciliary plasm and axoneme. Furthermore, we found significantly BC-associated genes involved in RNA-related processes, including e.g., genes in the integrator complex.ConclusionsHere, we identified genes and pathways associated with real-life kidney BC particle load, indicating alterations in gene expression involved in assembly and maintenance of primary cilia, the anti-inflammatory properties of the innate immune system, and DNA damage-related pathways. These findings highlight the need for public health measures to reduce exposure and protect kidney health in at-risk populations.