155 Chan Mir ##BEST##

Background and aim: Pathogenetic mechanisms underlying albuminuria are not completely understood. Heavy metals might lead to atherosclerosis and kidney damage. miR-21, 126, 155 and 221 regulated endothelial function and might contribute to the development of albuminuria. To date, no clinical trial has explored the relationship between miRNAs, microalbuminuria and heavy metals in human. In this study, we aimed to examine the association between microalbuminuria, miRNAs and heavy metals in adolescents.

155 Chan Mir

Conclusion: The results of our study suggest an association between microalbuminuria, miR-21 and heavy metals (arsenic and lead). This might imply that miR-21 is involved in the pathogenetic mechanisms linking heavy metals exposure and albuminuria.

To determine how miR-155 affects the phenotype and function of CD14+ monocytes, we transfected healthy control PBM with either miR-155 or negative control mimic (miR-CTR). Transfection with miR-155 resulted on average in 33% transfected cells and led to significant upregulation of mature miR-155 transcript levels (Supplementary Figure 4) and increased cell survival (not shown), as we previously reported [18]. Following transfection, we sorted live monocytes based on live/dead dye staining and FSChi CD14high expression thereby enriching for transfected cells (Supplementary Figure 2). RNA was extracted and bulk RNA-seq (n = 5 per condition) was performed to explore the transcriptional changes induced by miR-155 in myeloid cells. RNA-seq analysis (adjusted P

The production of high-affinity antibodies by B cells is essential for pathogen clearance. Antibody affinity for antigen is increased through the affinity maturation in germinal centers (GCs). This is an iterative process in which B cells cycle between proliferation coupled with the acquisition of mutations and antigen-based positive selection, resulting in retention of the highest-affinity B cell clones. The posttranscriptional regulator microRNA-155 (miR-155) is critical for efficient affinity maturation and the maintenance of the GCs; however, the cellular and molecular mechanism by which miR-155 regulates GC responses is not well understood. Here, we utilized a miR-155 reporter mouse strain and showed that miR-155 is coexpressed with the proto-oncogene encoding c-MYC in positively selected B cells. Functionally, miR-155 protected positively selected c-MYC+ B cells from apoptosis, allowing clonal expansion of this population, providing an explanation as to why Mir155 deletion impairs affinity maturation and promotes the premature collapse of GCs. We determined that miR-155 directly inhibits the Jumonji family member JARID2, which enhances B cell apoptosis when overexpressed, and thereby promotes GC B cell survival. Our findings also suggest that there is cooperation between c-MYC and miR-155 during the normal GC response, a cooperation that may explain how c-MYC and miR-155 can collaboratively function as oncogenes.