Netrins &amp; Semaphorins: Novel regulators of the immune response

Feinstein, Jordyn; Ramkhelawon, Bhama

doi:10.1016/j.bbadis.2017.09.010

Cited by 24 publications

(22 citation statements)

References 75 publications

(81 reference statements)

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“…Because the TGF-β canonical and non-canonical signaling pathways overlap with a number of pathway terms highly enriched in our PPI network 34 , 37 , our results provide evidence for the involvement of the TGF-β superfamily in the development of CLD in CDH newborns, providing support to the hypothesis that a primary disruption in lung vasculature and airway development accompany the diaphragmatic defect in CDH, and that the extent of the resulting cardiopulmonary dysfunction contributes to the development of CLD in CDH newborns. Further support to this hypothesis is found through our observation that major genes participating in the semaphorin signaling, involved in development and regulation of immune responses through guidance cues 38 , 39 , are predicted targets of the miRNAs we found dysregulated in blood of CDH children with severe outcomes.…”

Section: Discussionsupporting

confidence: 70%

Circulating microRNAs are associated with Pulmonary Hypertension and Development of Chronic Lung Disease in Congenital Diaphragmatic Hernia

Herrera-Rivero

Zhang

Heilmann‐Heimbach

et al. 2018

Sci Rep

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Pulmonary hypertension (PH) contributes to high mortality in congenital diaphragmatic hernia (CDH). A better understanding of the regulatory mechanisms underlying the pathology in CDH might allow the identification of prognostic biomarkers and potential therapeutic targets. We report the results from an expression profiling of circulating microRNAs (miRNAs) in direct post-pulmonary blood flow of 18 CDH newborns. Seven miRNAs differentially expressed in children that either died or developed chronic lung disease (CLD) up to 28 days after birth, compared to those who survived without developing CLD during this period, were identified. Target gene and pathway analyses indicate that these miRNAs functions include regulation of the cell cycle, inflammation and morphogenesis, by targeting molecules responsive to growth factors, cytokines and cellular stressors. Furthermore, we identified hub molecules by constructing a protein-protein interaction network of shared targets, and ranked the relative importance of the identified miRNAs. Our results suggest that dysregulations in miRNAs let-7b-5p, -7c-5p, miR-1307-3p, -185-3p, -8084, -331-3p and -210-3p may be detrimental for the development and function of the lungs and pulmonary vasculature, compromise cardiac function and contribute to the development of CLD in CDH. Further investigation of the biomarker and therapeutic potential of these circulating miRNAs is encouraged.

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Section: Discussionsupporting

confidence: 70%

Circulating microRNAs are associated with Pulmonary Hypertension and Development of Chronic Lung Disease in Congenital Diaphragmatic Hernia

Herrera-Rivero

Zhang

Heilmann‐Heimbach

et al. 2018

Sci Rep

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“…Semaphorins play important roles in guiding immune responses ( 95 ). We found certain semaphorins to be selectively transcribed by DC and monocyte subsets.…”

Section: Discussionmentioning

confidence: 99%

Precise Delineation and Transcriptional Characterization of Bovine Blood Dendritic-Cell and Monocyte Subsets

et al. 2018

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A clear-cut delineation of bovine bona fide dendritic cells (DC) from monocytes has proved challenging, given the high phenotypic and functional plasticity of these innate immune cells and the marked phenotypic differences between species. Here, we demonstrate that, based on expression of Flt3, CD172a, CD13, and CD4, a precise identification of bovine blood conventional DC type 1 and 2 (cDC1, cDC2), plasmacytoid DC (pDC), and monocytes is possible with cDC1 being Flt3+CD172adimCD13+CD4−, cDC2 being Flt3+CD172a+CD13−CD4−, pDC being Flt3+CD172adimCD13−CD4+, and monocytes being Flt3−CD172ahighCD13−CD4−. The phenotype of these subsets was characterized in further detail, and a subset-specific differential expression of CD2, CD5, CD11b, CD11c, CD14, CD16, CD26, CD62L, CD71, CD163, and CD205 was found. Subset identity was confirmed by transcriptomic analysis and subset-specific transcription of conserved key genes. We also sorted monocyte subsets based on their differential expression of CD14 and CD16. Classical monocytes (CD14+CD16−) clustered clearly apart from the two CD16+ monocyte subsets probably representing intermediate and non-classical monocytes described in human. The transcriptomic data also revealed differential gene transcription for molecules involved in antigen presentation, pathogen sensing, and migration, and therefore gives insights into functional differences between bovine DC and monocyte subsets. The identification of cell-type- and subset-specific gene transcription will assist in the quest for “marker molecules” that—when targeted by flow cytometry—will greatly facilitate research on bovine DC and monocytes. Overall, species comparisons will elucidate basic principles of DC and monocyte biology and will help to translate experimental findings from one species to another.

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“…Netrins play a role in axonal guidance including development of mammary gland, lung, pancreas, and blood vessels, inhibition of leukocyte migration and chemoattraction of endothelial cells. 125 Netrin-1 is a potent inhibitor of leukocyte chemoattraction. The kidney has high levels of netrin expression.…”

Section: Netrinmentioning

confidence: 99%

Biomarkers of Drug-Induced Kidney Toxicity

Griffin

Faubel²,

Edelstein³

2019

Therapeutic Drug Monitoring

180

125

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Blood urea nitrogen (BUN) and serum creatinine are imperfect markers of kidney function because they are influenced by many renal and non-renal factors independent of kidney function. A biomarker that is released directly into the blood or urine by the kidney in response to injury may be a better early marker of drug-induced kidney toxicity than BUN and serum creatinine. Urine albumin and urine protein, as well as urinary markers kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, clusterin, and trefoil factor-3 (TFF-3) have been accepted by the Food and Drug Administration (FDA) and European Medicines Agency as highly sensitive and specific urinary biomarkers to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Other biomarkers of drug-induced kidney toxicity that have been detected in the urine of rodents or patients include IL-18 (interleukin-18), NGAL (neutrophil gelatinase-associated lipocalin), Netrin-1, liver type fatty acid binding protein (L-FABP), urinary exosomes, and TIMP2 (insulin-like growth factor-binding protein 7)/IGFBP7 (insulin-like growth factor binding protein 7), also known as NephroCheck®, the first FDA-approved biomarker testing platform to detect acute kidney injury (AKI) in patients. In the future, a combined use of functional and damage markers may advance the field of biomarkers of drug kidney toxicity. Earlier detection of drug-induced kidney toxicity with a kidney specific biomarker may result in the avoidance of nephrotoxic agents in clinical studies and may allow for earlier intervention to repair damaged kidneys.

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Netrins & Semaphorins: Novel regulators of the immune response

Cited by 24 publications

References 75 publications

Circulating microRNAs are associated with Pulmonary Hypertension and Development of Chronic Lung Disease in Congenital Diaphragmatic Hernia

Circulating microRNAs are associated with Pulmonary Hypertension and Development of Chronic Lung Disease in Congenital Diaphragmatic Hernia

Precise Delineation and Transcriptional Characterization of Bovine Blood Dendritic-Cell and Monocyte Subsets

Biomarkers of Drug-Induced Kidney Toxicity

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