Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo

Abstract

Changes in miRNA expression of glomerular capillaries during antibody-mediated rejection (ABMR) are poorly understood and could contribute to the deleterious inflammation and fibrosis of ABMR via suppression of target genes. A better understanding could lead to novel diagnostic tools and reveal novel therapeutic targets. We explored deregulated miRNAs in an glomeruloendothelial in vitro model of ABMR due to class I human leukocyte antigen (HLA) with and without complement activation. We studied a set of 16 promising candidate miRNAs in microdissected glomeruli a confirmation set of 20 human transplant biopsies (DSA+) compared to 10 matched controls without evidence for ABMR. Twelve out of these 16 glomerulocapillary miRNAs could successfully be confirmed as dysregulated in vivo with 10 upregulated (let-7c-5p, miR-28-3p, miR-30d-5p, miR-99b-5p, miR-125a-5p, miR-195-5p, miR-374b-3p, miR-484, miR-501-3p, miR-520e) and 2 downregulated (miR29b-3p, miR-885-5p) in DSA+ vs. controls. A random forest analysis based on glomerular miRNAs identified 18/20 DSA+ and 8/10 controls correctly. This glomerulocapillary miRNA signature associated with HLA class I-DSA could improve our understanding of ABMR and be useful for diagnostic or therapeutic purposes.

Evaluation of recombination losses in thin film solar cells using an LED sun simulator − the effect of RbF post-deposition on CIGS solar cells

“…The PL spectra recorded from both layers are shown in Figure S2. The exponential slope of the PL signal gives the sub-gap tail energy [19], which is mainly influenced by shallow defects and compositional disorder [10]. It is 25 meV for the non-treated layer and 20 meV for the RbF treated layer.…”

“…CIGS absorber layers were prepared onto molybdenum coated glass substrates using a multi-stage evaporation process as described in detail in [10]. The substrate temperature was kept at 300°C and 530°C during the first and following stages of the process, respectively.…”

Diagnostic, Prognostic, and Therapeutic Value of Non-Coding RNA Expression Profiles in Renal Transplantation

“…They validated five miRNAs (miR-99b, miR-23b, let-7b-5p, miR-30a, and miR-145) from a panel of twenty-five miRNAs whose expression was statistically different between acute pyelonephritis and AR [51]. TGF-β has been associated with susceptibility to recurrent urinary tract infections in humans [52]. Interestingly, some of the miRNAs from the acute pyelonephritis signature modulate TGF-β signaling pathways, which could hint to their role in fibrosis and renal scarring progression [61,62,[84][85][86].…”

“…Moreover, this miRNA signature could discriminate patients with consistent IF/TA-like miRNA changes that correlated with histological findings even when their serum creatinine and estimated glomerular filtration rate measurements indicated normal renal function. Heinemann FM et al proposed a miRNA signature associated with human leukocyte antigens (HLA) class I-donor specific antibodies (DSA) in microdissected glomeruli of 20 human transplant biopsies after studying a set of sixteen candidate miRNAs initially discovered in a glomeruloendothelial in vitro model of ABMR [52]. Ten miRNAs were upregulated (let-7c-5p, miR-28-3p, miR-30d-5p, miR-99b-5p, miR-125a-5p, miR-195-5p, miR-374b-3p, miR-484, miR-501-3p, and miR-520e) and two downregulated (miR29b-3p and miR-885-5p) in DSA-positive transplant recipients, compared to matched controls without ABMR.…”

Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases

“…It was reported that the miRNA/miRNA* ratio may vary between multiple tissue samples, probably due to changes in miRNA* degradation [ 6 ], and, in some cases, even strand dominance may change [ 7 ]. For example, hsa-let-7a* was downregulated in fibroblasts infected with varicella zoster virus [ 8 ], and mir-374b* was upregulated during antibody-mediated renal graft rejection [ 9 ]. Approximately 70% of all miRNAs are expressed in the liver.…”